NM_006231.4:c.6531+19G>T is an intronic variant located 19 base pairs downstream of POLE exon 46. It is not a null variant (nonsense, frameshift, or canonical splice site) and therefore does not meet PVS1 criteria (PMC6185798).¹ The variant is completely absent from all queried population databases including gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada, meeting PM2 at the supporting level.² SpliceAI predicts no significant splicing impact (max delta score = 0.02), meeting BP4 at the supporting benign level.³ The León-Castillo et al. 2020 custom POLE framework, which customizes PM1, PS4, PP3, and BP4, applies exclusively to exonuclease-domain missense variants represented in its supplementary tables. This intronic variant is absent from those tables and none of the custom criterion specifications are triggered.⁴ The variant is absent from ClinVar and COSMIC, and no functional studies, case reports, de novo events, or segregation data have been identified for this variant.⁵ With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the overall evidence is equivocal. The criteria do not reach the threshold for Likely Pathogenic, Pathogenic, Likely Benign, or Benign classification. This variant is classified as a Variant of Uncertain Significance (VUS).⁶