In contrast. nonconserved positions are sel??dom mu??tated in the lab. even though they often comprise >50% of the positions in a sequence align??ment. Moreover. nonconserved posi??tions can make impor??tant contributions to function: Pro??tein paralogs evolve functional variation via chan??ges at noncon??served positions; changes at noncon??served positions also cause disease.refPYK We hypo??thesized that. for a subset of nonconserved positions. the assumptions above give rise to false mutation predictions.