NM_000264.5:c.1641C>T is a synonymous variant (p.Ser547=) in PTCH1 with no predicted impact on splicing (SpliceAI max delta=0.00).¹ This variant is present at high frequency in population databases: gnomAD v2.1 AF=0.798% (2242/281002 alleles, including 17 homozygotes) and v4.1 AF=1.125% (18153/1613520 alleles, including 125 homozygotes), exceeding the BA1 (>1%) and BS1 (>0.3%) thresholds for an autosomal dominant disorder with full penetrance expected at an early age.² The observation of 17 homozygotes in gnomAD v2.1 and 125 homozygotes in gnomAD v4.1 is incompatible with a fully penetrant autosomal dominant condition; this alone is strong evidence for a benign classification (BS2).³ ClinVar classifies this variant as Benign based on submissions from 14 clinical laboratories; this represents a reputable source reporting a benign classification (BP6).⁴ The variant was identified as a non-pathogenic synonymous polymorphism (rs2066830, p.S547S) in a study of 78 sporadic medulloblastoma cases and in ovarian tumor/control cohorts, consistent with a benign interpretation.⁵ Computational evidence (SpliceAI) predicts no splicing impact; combined with its synonymous nature, this supports a benign interpretation (BP4, BP7).⁶ The BA1 criterion is met at stand-alone benign strength: allele frequency >1% in multiple gnomAD populations is incompatible with a highly penetrant dominant disorder. Per ACMG/AMP 2015 combination rules, meeting BA1 alone is sufficient for a Benign classification regardless of other criteria.⁷