NM_198253.2:c.833C>T (p.Pro278Leu) in TERT is a rare missense variant with extremely low population frequency (gnomAD v2.1 AF=9.83e-6, v4.1 AF=3.77e-6), meeting PM2 at supporting strength.¹ Multiple in silico predictors (REVEL 0.137, BayesDel -0.245, SpliceAI max delta 0.02) consistently suggest no damaging effect on the gene product, meeting BP4 at supporting benign strength.² This variant has been reported in ClinVar as Likely benign by a single clinical laboratory (Labcorp Genetics/Invitae, 1-star review status, SCV000824613). The classification and review status do not meet thresholds for PP5 or BP6 application under the 3-star expert panel requirement.³ No variant-specific functional data, de novo observations, segregation data, case-control studies, or domain-level hotspot evidence were identified. OncoKB reports Unknown Oncogenic Effect. PM1 is not met as Pro278 is not in a statistically significant mutational hotspot.⁴ PVS1 is not applicable (missense variant outside null-variant buckets). PS1, PM5, BP7, BP3, PM3, and PM4 are not applicable due to variant type or absence of required evidence patterns.⁵ With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is in equipoise. The final classification under generic ACMG/AMP 2015 rules (Richards et al., PMID:25741868) is Variant of Uncertain Significance (VUS).⁶