Say I have a REST API with endpoint
405 Method Not Allowed
404 Not Found
If, at the moment a request is received, a resource (regardless of the concept that it represents) does not support a particular method (POST), the correct response to return is
The 405 (Method Not Allowed) status code indicates that the method received in the request-line is known by the origin server but not supported by the target resource. The origin server MUST generate an Allow header field in a 405 response containing a list of the target resource's currently supported methods.
The HTTP Specification includes a method (OPTIONS) and response headers (Allow) that enable a client to interrogate a server to discover what methods are permitted. Adoption might be lacking, although I suppose CORS changes that.
Note: there are use cases where POST to a singular resource is a reasonable option (consider how you would define the protocol to star a responsitory in an api where HTML was your hypermedia format). In that case, you should choose the appropriate success code (200, 201, 204...), assuming things went well, of course.