Thus, while our study is far from comprehensive in studying potential impacts of human ACE2 missense variants on SARS-CoV or SARS-CoV-2 spike mediated entry, the collective rarity of ACE2 missense germline variation in humans suggests that they will likely have only limited effect on SARS-CoV-2 entry and infection at the population level. This evidence concerns the gene ACE2 and infection.