NM_000264.5:c.4033C>G (p.Arg1345Gly) is a missense variant in PTCH1, a gene in which loss-of-function variants cause Gorlin syndrome (nevoid basal cell carcinoma syndrome) via an autosomal dominant haploinsufficiency mechanism. This variant is present at extremely low frequency in gnomAD v2.1 (AF=0.00081%, 2/246054 alleles) and gnomAD v4.1 (AF=0.00025%, 4/1611580 alleles), meeting PM2_Supporting (ClinGen SVI threshold ≤0.002%).¹ Computational predictors are uninformative or weakly benign: BayesDel score is -0.078 (benign range), SpliceAI delta is 0.00, and REVEL is not available. This does not meet thresholds for PP3 or BP4.² In ClinVar, Labcorp Genetics (formerly Invitae) has classified this variant as Benign (SCV001497416, criteria provided), while Ambry Genetics has classified it as Uncertain significance (SCV002619761). The Benign classification from a reputable clinical laboratory supports BP6_Supporting.³ No functional studies, segregation data, de novo reports, case-control data, or variant-specific publications were identified for this variant. PVS1, PS1-PS5, PM1, PM5, PM6, PP1-PP5, and the benign criteria BA1, BS1-BS4, BP1-BP2, BP4-BP5, BP7 are either not met or not applicable. The evidence profile yields one supporting pathogenic criterion (PM2_Supporting) and one supporting benign criterion (BP6_Supporting). Per generic ACMG/AMP 2015 combination rules (PMID:25741868), conflicting evidence with equal weight on both sides results in a classification of Variant of Uncertain Significance (VUS).⁴