You should consider if you really want to integrate your application super tightly with the HTTP protocol.
Will it always be used exclusively over a REST-ful HTTP API that you control, and it has exactly one hop to the client, or passes through hops that can be trusted to never alter the HTTP metadata significantly? In that case you can afford to make HTTP codes semantically relevant for your app.
But maybe you need to pass data through multiple different types of layers and different mechanisms (socket protocols, pub-sub, file storage etc.) In that case you want all your semantics to be independent from any form of transport.