If you provide me with a self-contained code example (with data required to run it) that is “too slow”, I’d be willing to try and optimise it to support my point above.
Also, have you tried Numba? It maybe a matter of just applying a “@jit” decorator and restructuring your code a bit in which case it may get magically boosted a few hundred times in speed.
[1] https://git.embl.de/costea/metaSNV/blob/master/metaSNV_post....