NM_001048171.1:c.995C>T (p.Ser332Leu) is a missense variant in exon 12 of MUTYH, a gene associated with autosomal recessive MUTYH-associated polyposis (MAP). The variant is present at very low frequency in gnomAD (v2.1 AF=0.00512%; v4.1 AF=0.00348%), with no homozygous observations, consistent with PM2 supporting evidence.¹ Multiple in silico prediction tools concordantly predict a benign effect: REVEL score 0.116 (below 0.5 threshold), BayesDel score -0.476 (predicting benign), and SpliceAI predicts no splicing impact (max delta 0.00). This supports BP4 criteria.² ClinVar submissions predominantly classify this variant as Uncertain significance (7/11 submitters). One clinical laboratory (Ambry Genetics) classifies it as Likely benign. No expert panel classification has been issued.³ Functional evidence from D'Agostino et al. 2009 (PMID:19092703) suggesting reduced glycosylase activity for p.S332L was identified through exploratory search but could not be independently verified as full-text was not available in the case materials. This evidence was not applied. Overall, one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4) are met, placing this variant in the VUS (Variant of Uncertain Significance) category under generic ACMG/AMP 2015 combination rules.⁴