Population frequency has been one of the most widely used criteria to help assign pathogenicity to newly described mitochondrial DNA variants. However, after sequencing this molecule in thousands of healthy individuals, it has been observed that a very large number of genetic variants have a very low population frequency, which has raised doubts about the utility of this criterion. By analyzing the genetic variation of mitochondrial DNA-encoded genes for oxidative phosphorylation subunits in 195,983 individuals from HelixMTdb that were not sequenced based on any medical phenotype, we show that rare variants are deleterious and, along with other criteria, population frequency is still a useful criterion to assign pathogenicity to newly described variants.
Keywords: Mitochondrial DNA; Pathological variants; Population frequency.
© 2022. The Author(s).