Do you have any links for the last paragraph? I know that there can be two gene encoded in reverse in bacteria but have no knowledge of any frame-shifted transl

Do you have any links for the last paragraph? I know that there can be two gene encoded in reverse in bacteria but have no knowledge of any frame-shifted translations? About the second paragraph: well, it was not really thought that differences are always detrimental to health, and there is quite a number of variant prioritization tools out there that try to find those variants that are causal compared to all the silent/no-effect mutations (mostly for comparing humans but also somatic).