This variant is a missense change (p.Arg638His) in PTCH1, a gene in which loss-of-function is an established mechanism for Gorlin syndrome (nevoid basal cell carcinoma syndrome), an autosomal dominant disorder with high penetrance and early onset.¹ The variant is present in gnomAD population databases at low frequency overall (v2.1: 33/282,644 alleles, AF=0.012%; v4.1: 126/1,613,872 alleles, AF=0.008%), with the highest subpopulation frequency in Africans/African Americans (0.112% in v2.1). No homozygotes have been observed.² The variant meets PM2 at supporting level: overall allele frequency is below the 0.1% threshold, though the African subpopulation frequency is borderline (0.112% in v2.1).³ Five of six clinical diagnostic laboratories in ClinVar classify this variant as Likely benign or Benign (ClinVar ID 220182), providing supporting evidence for a benign interpretation (BP6_supporting).⁴ Multiple in silico predictors support a benign effect: REVEL score 0.378, BayesDel score -0.243824, and SpliceAI predicts no splicing impact (max delta 0.05). These provide supporting benign evidence (BP4_supporting).⁵ The variant has been observed in multiple individuals in gnomAD presumed to be healthy adults, which is inconsistent with a fully penetrant early-onset dominant disorder such as Gorlin syndrome, providing additional supporting benign evidence (BS2_supporting).⁶ No pathogenic evidence criteria were met: there is no functional data supporting a damaging effect (PS3 not met), no case-control enrichment (PS4 not met), no de novo reports (PS2/PM6 not met), no segregation data (PP1 not met), the variant is not in a known hotspot or critical domain (PM1 not met), and no reputable source reports it as pathogenic (PP5 not met).⁷ No functional studies of p.Arg638His or a systematically characterized range including this residue were identified. The variant has not been experimentally characterized for its effect on Hedgehog signaling, PTCH1-SMO interaction, or protein trafficking.⁸