NM_198253.2:c.2509C>T (p.Leu837Phe) is a rare missense variant in the TERT gene that is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada (PM2_Supporting).¹ This variant has been reported in ClinVar as a Variant of Uncertain Significance by a single clinical laboratory (Labcorp/Invitae, SCV003459151).² No variant-specific functional studies, case-control data, de novo observations, segregation data, or same-residue pathogenic comparators were identified for this variant.³ In silico predictions are conflicting: REVEL predicts a deleterious effect (0.735), while BayesDel predicts a benign effect (0.123), and SpliceAI predicts no splicing impact (delta = 0.00).⁴ TERT loss-of-function is an established disease mechanism for autosomal dominant dyskeratosis congenita and related telomere biology disorders, and both truncating and missense variants have been reported as pathogenic in the literature.⁵ Applying generic ACMG/AMP 2015 classification rules (PMID:25741868), only one supporting criterion (PM2) is met, with no benign criteria met. This is insufficient to classify as Likely Pathogenic or Likely Benign, resulting in a final classification of Variant of Uncertain Significance (VUS).⁶