UPF1 and cancer: Although it is difficult to conclusively prove that a specific genetic change does not promote cancer, we were unable to detect biological or molecular changes arising from two mutations reported by Liu et al. UPF1’s status as an essential gene and our discovery that many reported UPF1 mutations occur as germline genetic variants of no known pathogenicity together suggest that other UPF1 mutations reported by Liu et al. could similarly represent genetic differences that do not functionally contribute to PASC.