NM_000264.5(PTCH1):c.431G>A (p.Arg144His) is a missense variant in PTCH1, a gene associated with autosomal dominant Gorlin syndrome (nevoid basal cell carcinoma syndrome).¹ This variant is exceedingly rare in population databases, with an allele frequency of approximately 4.0e-6 in both gnomAD v2.1 (1/251,480 alleles) and v4.1 (7/1,614,112 alleles), and no homozygotes have been observed.² The variant has been reported in ClinVar (Variation ID 575795) as Uncertain Significance by three clinical laboratories and as Likely Benign by one laboratory; no expert panel classification is available.³ Computational predictors are mixed: REVEL scores 0.583 (borderline), BayesDel scores 0.231 (benign-leaning), and SpliceAI predicts no splicing impact (max delta 0.05).⁴ No variant-specific functional studies, segregation data, de novo observations, case-control data, or reputable pathogenic classifications are available for this variant. Applying generic ACMG/AMP 2015 criteria (PMID:25741868), only PM2 (supporting) is met. With a single supporting pathogenic criterion and no benign criteria met, the final classification is a Variant of Uncertain Significance.⁵