NM_001040108.2:c.20T>A (p.Val7Asp) is a missense variant in exon 2 of MLH3, a DNA mismatch repair gene associated with autosomal dominant Lynch syndrome and autosomal recessive polyposis predisposition. This variant is absent from gnomAD v2.1 and v4.1 population databases, supporting PM2 at a supporting strength level.¹ Multiple computational predictors do not support a deleterious effect: REVEL score is 0.384 (intermediate), BayesDel is −0.281 (benign-leaning), and SpliceAI predicts no splice impact (max delta 0.00). PP3 is not met.² The variant has been reported once in ClinVar as Uncertain significance by a single clinical laboratory (Ambry Genetics; Variation ID 1785889); no pathogenic or benign consensus exists.³ No variant-specific functional studies, case-control data, cosegregation evidence, or de novo observations were identified for this variant in the available evidence sources. The PVS1 criterion is not applicable as this is a missense change (p.Val7Asp) that does not meet the ClinGen SVI PVS1 null-variant criteria (PMC6185798).⁴ The variant has been observed once in a somatic cancer context (COSMIC COSV53136280), which is not directly informative for germline pathogenicity classification.