NM_006231.3:c.1763T>C (p.Val588Ala) is a missense variant in POLE, the catalytic subunit of DNA polymerase epsilon. It is absent from gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_Supporting).¹ Multiple computational predictors suggest a benign effect: REVEL score 0.26, BayesDel score -0.437986, and SpliceAI delta score 0.00 (BP4_Supporting).² Residue 588 lies outside the POLE exonuclease domain (residues ~268–471) and is not one of the established pathogenic hotspot residues identified by León-Castillo et al. 2020. The variant is absent from COSMIC and has not been reported as a recurrent somatic mutation in endometrial carcinoma.³ No variant-specific functional data, de novo observations, co-segregation data, or ClinVar classifications were identified for this variant. OncoKB reports an unknown oncogenic effect with no variant-level curated evidence.⁴ The overall evidence profile yields PM2_Supporting (1 pathogenic supporting criterion) and BP4_Supporting (1 benign supporting criterion). These offset to a variant of uncertain significance (VUS) per ACMG/AMP 2015 classification rules.