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We literally spent trillions in the past century building doomsday machines -- hydrogen bombs and ICBMs -- to literally, intentionally destroy humanity as part of the MAD defensive strategy in the Cold War. That stuff is largely still out there. If anything suddenly kills humanity, that's high on the list of possibilities.

The other huge existential risk is someone intentionally creating a doomsday bug. Think airborne HIV with a long incubation period, or an airborne cancer causing virus. Something that would spread far and wide and cause enough debilitation and death that it leads to the collapse of civilization, then continues to hang around and kill people post-collapse (with no health care) to the point that the human race is in long term danger of extinction.

Both of those are extremely plausible to the point that the explanation for why they haven't happened yet is "nobody with the means has been that evil yet."