NM_000535.7:c.14A>T (p.Glu5Val) is a missense variant in exon 1 of PMS2. It is extremely rare in population databases (gnomAD v4.1: 8/1,612,464 alleles, AF=4.96e-06), meeting PM2_Supporting per InSiGHT/ClinGen PMS2 VCEP v2.0.0.¹ Multiple in silico predictors support a benign effect: the HCI prior probability for pathogenicity is 0.004 (meeting BP4_Supporting), REVEL score is 0.498, BayesDel score is 0.008, and SpliceAI predicts no splicing impact (max delta = 0.00).² No functional data, segregation data, de novo observations, or tumor phenotype data (MSI/IHC) are available for this variant. ClinVar reports this variant as Uncertain Significance (VCV231310, 7 submitters, criteria provided single submitter).³ The variant does not meet criteria for PVS1 (missense, not a null variant), PS1 (no same-amino-acid pathogenic comparator), PS3 (no functional data), PM5 (no same-residue pathogenic comparator), or any other pathogenic criterion. The only criteria met are PM2_Supporting (extremely rare in gnomAD) and BP4_Supporting (benign in silico predictions including HCI prior <0.11). With one pathogenic supporting and one benign supporting criterion, the evidence is insufficient to reach a Likely Pathogenic or Likely Benign classification under the VCEP combining rules. The variant remains a Variant of Uncertain Significance.⁴