Let's say that everyone on Earth disappears or dies spontaneously - except for one person. What would a plausible reason for this be?
Note that this isn't something gradual, like a disease wiping out Earth's population, but instead something that happens overnight. I am not looking for fantasy answers, but more realistic or sci-fi answers.
This takes place around 2022, or at most 2037, and the protagonist is in San Francisco, California.
200 designated survivors
Suppose there is an apocalyptic scenario on the horizon: in six months, e.g. a red giant only six light years away will go supernova. Scientists have already known that for a few years, but everything is kept secret to prevent panic. Your scientists haven't found any solution that would allow Earth's population to survive. It is estimated Earth will become uninhabitable for at least a century. They consider to preserve the human race, by sending out a space ship with a mixed population of ca 200 humans, initially in hibernation, to find shelter behind Jupiter for several months, to wait out the effects of the supernova.
The pilot made a mistake
At some point underway to Jupiter, your pilot accidentally touches a switch, which is decompressing the stasis compartments, exposing them to space. The stasis containers break. Everyone in hybernation dies, only the pilot survives. Watching the Earth burn.. A lonely and desperate human.
Female
It will depend on your story what happens next. Earth is dead now, there were a few other humans in space (ISS), but they don't have the means to survive. When the pilot is male, it would certainly be the end of mankind. Your evacuation ship could have a female pilot. She'll improvise with frozen sperm, to get herself pregnant.. Best case, she knows about the subject of genetics and pick some diversity (say, 6-7 children from different sperm samples).
(supplement)
Some notes about surviving a supernova on Earth
Putting the above answer, I had not realized your survivor protagonist resides in California. To work that out for my scenario.. First, to get an idea of the effects,
https://earthsky.org/astronomy-essentials/safe-distance-from-a-supernova-earth/
Supernova - 30 light years
.. on 30 light years distance, the oceans would be depleted of food and the atmosphere and O3 layer will be destroyed. Mass extinction follows. But that would not immediately result in a complete wipe out of civilization. Humans will manage below the surface, plans could be in place to restore the Ozone layer in some way (hand wave) and after some time, your planet would get repopulated with humans. After spending a century or two underground, part of Earth's surface and Earth's atmosphere would have to be re-terraformed to repair the damage ! In this case, there would be millions of survivors. 30 light years won't do, for a plausible single survivor.
Supernova - 6 light years
Now suppose the Supernova would occur at only 6 light years distance, like I've proposed, the Earth would be within the Supernova radius itself. That would not allow survival on Earth, I assumed zero human survivors on Earth.
Huge effects, like deadly X-Ray and gamma radiation spikes, electrocuting EMP's.. and after 3-5 years, you'll get core fragments and debris impacting on Earth. A Russian roulette, that could yield a ravaged Solar system.
All humans on Earth will have become infertile, due to the excessive radiation. Now, some families in California could have survived undergrounds, when lucky. Most will die, because they can't return to the surface. Maybe someone very smart invents a way, to keep his family alive longer.. The youngest son could survive his family for ca. 60 years and become the (very) lonely single human surviving on Earth.
What if all the other people had a car accident, slipped on some ice or choked on their food? And died as a result? The same day?
This would be highly unlucky, but not at all impossible. We all know single accidents happen, and if they are considered independent events it's simply a matter of probability. We all know that rolling two sixes with a pair of dice is possible, and many of us have rolled three or even four simultaneous sixes. If you keep at it long enough, sooner or later you will roll all sixes even if you throw a hundred simultaneous dice. Most of the times it will be later sooner than sooner (a lot later), but in principle it could happen on the first try.
Consulting Wikipedia, the average yearly mortality in traffic is 19 deaths per 100 000 people per year. That's a $\frac{\frac{19}{365}}{100~000}$ chance a given random person will die in traffic any given day. As a first approximation, the probability of 8 billion people randomly dying in traffic should thus be around $\left(\frac{\frac{19}{365}}{100~000}\right)^{8~000~000~000} \approx 9.35048 \cdot 10^{-50~268~314~109}$.
And that's just traffic! If you include other kinds of accidents, you can get the probability way down. You could also have a few nukes accidentally go off in Europe, let a few meteors kill off the Africans and have a terrible gas leakage for most of the Chinese. If we are very unlucky, these disasters happen the same day. With some optimisation you could probably (no pun intended) even shave the exponent in my final number down to 40 billion or so.
It's still extremely unlikely, but not impossible. I'd finish by saying "stranger things have happened", but in this case they literally haven't.
Someone has unleashed killer robots who kill everyone except for one person. Perhaps that one person is the inventor, the inventor's love interest, or maybe just someone named Null.
A realistic answer here is simulation theory. According to Wikipedia, the simulation hypothesis, in a nutshell, is the idea that our world is a simulation.
Your protagonist is living a simulation. The civilization simulating the world has ulterior motives and is probably somewhere between a 2 and a 3 on the Kardashev scale, which is far enough that humanity (about a 0.72) may not be complex enough to understand them; kind of like explaining human society to a very smart ant.
The simulating civilization has reasons to simulate humanity, and even to remove everyone from existence except for one person. There's also no reason that the protagonist should know the reasons for which they are being simulated.
For more details, you can see these videos from a channel called Kurzgesagt (no affiliation):
Have a massive comet hit the earth, and kill everyone on it, and most people in the ISS and such.
Someone who has gone to space on the other side of the planet would be fine. They can return to earth and be the last person alive.
Your protagonist could be involved with some kind of experimental container / field technology, and inside of something that incidentally happens to give them protection from some other freak event, although picking something significant enough to kill everyone in one day without completely destroying the earth in general is difficult. Anything that would kill all the people that quickly is also very likely to kill all the plants and animals, and your survivor is not going to last very long, unless you can come up with something human-targeted. Perhaps a self replicating nanobot virus with a high infection rate and a specified self destruct date (or that receives a signal to self destruct, if for example it is an alien weapon).
One-day-destruction doesn't sound very plausible to me, however.
Lets say we have a person who has a particularly strange birth mark.
Creating this, weird pattern around his or her face. But this pattern, forms an Adversarial machine learning image.
https://en.wikipedia.org/wiki/Adversarial_machine_learning
Basically, this birth mark hides the person from visual recognition devices. And, lets say Rogue AI's tried to destroy humanity and only the humanity. But lack of energy facility workers and bombing during the war, caused AI's to lose their energy source.
Now, this virtually invisible person can easly trick currently operating machines by messing up visual recognition systems and can go on with whatever plot you want.
Add a bit more background to your protogonist by making that person knowledgable in AI's and let that person develop a make-up form, a cape, clothing or a tattoo that will mess up AI visual processing. And let the AI apocalypse hit the world while this pattern was not finished. So it can only work with this person's body structure.
It will work.
I was thinking about an uncurable virus and an experimental subject who was immune to this virus. Virus spread to humanity, killed everyone except this person now.
One option could be something from space, considering that you need the entire population except one person to disappear or die, it cannot be something that has effects on a slower scale like a meteor with a virus to which your protagonist is miraculously immune. A geomagnetic storm or something of a similar nature but on a scale that would affect the entire planet could work, something huge and with devastating effects on a scale greater than the Carrington Event, perhaps a weapon of some overdeveloped species that seeks to rid the Earth of the humanity that is destroying it, but with a 0.001% margin of error that makes it possible for a person to survive. The rest of the people would disappear or die without the rest of the planet being affected.
Another option could be a mega-earthquake that opens certain layer of the earth at a global level and makes some type of gas or disease escape to the outside that kills all those who didn't die from the damage that an earthquake implies. The protagonist could only remember that the earth began to move, and upon awakening among the rubble discover that everyone, even those who seemed to be safe in the streets, have died.
A last option is that your protagonist by some space-time rupture or similar is transported to a parallel world in which only he exists. It may be that in the middle of the night he feels sick, he feels like everything around him is distorted and when he wakes up there is no one but him.
Depending on the goals you have for your protagonist in the story (Does he want to find out what happened to the rest of the people? Does he want to live out his fantasies and live as if at any moment his life could also end? Does he go crazy?) the reason may or may not be so important, I suggest you have a clear idea first and then develop each idea.
