NM_198253.2:c.899G>A (p.Gly300Asp) is a rare missense variant in TERT that is absent from population databases, with 0 alleles observed across 1,571,010 alleles in gnomAD v4.1, meeting PM2 (moderate) criterion.¹ This variant has been reported in ClinVar as Uncertain Significance by a single clinical laboratory (Variation ID 2937435; Labcorp Genetics). The classification is based on 1-star review status and does not meet the 3-star expert panel threshold for PP5 or BP6.² In silico predictors are inconclusive: REVEL (0.283) is intermediate, BayesDel (-0.187) is marginally in the benign direction, and SpliceAI predicts no splicing impact (max delta 0.00). No consensus supports either pathogenicity (PP3) or benignity (BP4).³ No functional studies (PS3/BS3), case-control data (PS4), de novo observations (PS2/PM6), co-segregation data (PP1/BS4), or same-residue pathogenic comparators (PM5/PS1) are available for this variant.⁴ The variant is a missense substitution and does not qualify for PVS1 null-variant assessment.⁵ Based on the available evidence, this variant meets only one moderate pathogenicity criterion (PM2). Under the ACMG/AMP 2015 scoring framework, this alone is insufficient to classify the variant as Likely Pathogenic or Pathogenic. The variant remains a Variant of Uncertain Significance.⁶