It means that the server did not find a current representation of the resource and that the server accepts responsibility for providing an authoritative answer to whether it exists (if the latter is not the case, the most correct response is 421.) Aside from that and the combination of being unwilling to provide a default representation, not having a representation consistent with the Accept header provided by the client, and preferring not to distinguish this case from non-existence with a 406 response (which, like the situations to which 421 applies, is an edge case), the reason for a resource not being found is overwhelmingly that it does not, in fact, exist.

It is true that there are some other things that a 404 might mean, but “does not exist” is not only within the space of things covered by “Not Found”, it is by far the most common reason for it.