This variant is a missense substitution (NM_001128425.2:c.1255G>A, p.Ala419Thr) in exon 13 of MUTYH. The variant is present at very low frequency in gnomAD v2.1 (AF=0.00672%, 19/282,560 alleles, 0 homozygotes) and v4.1 (AF=0.00874%, 141/1,614,058 alleles, 1 homozygote), and is absent from gnomAD-Canada, meeting PM2 at the supporting level.¹ Multiple in silico tools predict no damaging effect: REVEL score 0.414 (below the 0.5 pathogenic threshold), BayesDel score -0.184886 (benign-leaning), and SpliceAI delta score 0.00 (no predicted splice impact), meeting BP4 at the supporting level.² No functional studies, segregation data, de novo observations, or variant-specific literature have been identified for this variant. The MUTYH VCEP (InSiGHT Hereditary Colorectal Cancer/Polyposis Specification v1.0.0) framework was present but incomplete with no gene-specific criteria rules; generic ACMG/AMP 2015 criteria were applied.³ In ClinVar, the variant is reported as Uncertain significance by 11 of 14 submitters. Ambry Genetics classifies as Benign and Labcorp/Invitae as Likely benign, though the underlying evidence is not publicly accessible. The single homozygote in gnomAD v4.1 warrants attention for a recessive disorder but lacks phenotype data.⁴ The only applicable criteria are PM2_supporting (pathogenic supporting) and BP4_supporting (benign supporting). These oppose each other, resulting in conflicting evidence insufficient to classify beyond Variant of Uncertain Significance (VUS).