SMG1 and pachyonychia congenita: Finally, the presence of a recurrent variant (i.e., c.103G>A) that associates with PC, in both the discovery and validation series, provides further support for the causal role of SMG1. While this variant may not alter protein function given the enriched MAF in the Asian and Latino populations and the presence of homozygotes in gnomAD, this variant may be in linkage disequilibrium with a pathogenic variant in Europeans, resulting in the association with PC observed in this European population.