NM_006231.4:c.3459+12G>T is a rare intronic variant in POLE located 12 bases downstream of exon 28.1 This variant is extremely rare in population databases, present at an allele frequency of 1.24e-6 (2/1,614,094 alleles) in gnomAD v4.1 and absent from gnomAD v2.1 (PM2_Supporting).2 SpliceAI predicts no splicing impact (max delta=0.0), and the variant lies outside the canonical splice consensus at the +12 intronic position (BP7_Supporting).3 This variant has been reported in ClinVar as Likely Benign by a single clinical laboratory (VariationID 1580883, 1-star review status), though the 1-star rating is insufficient for PP5 or BP6 application.4 No functional data, segregation data, de novo reports, or case-control evidence are available for this variant. The León-Castillo et al. 2020 custom POLE framework is exclusively missense-focused and does not provide applicable rules for this intronic variant.5 The variant has not been reported in somatic cancers (COSMIC) and is not a known hotspot (cancerhotspots.org negative). With PM2_Supporting (pathogenic) and BP7_Supporting (benign), the evidence is conflicting and insufficient to reach a likely benign or likely pathogenic classification. This variant is classified as a Variant of Uncertain Significance (VUS).