NM_198253.2:c.875C>T (p.Thr292Met) is a missense variant in exon 2 of TERT. TERT is associated with autosomal dominant and recessive telomere biology disorders including dyskeratosis congenita, bone marrow failure, and pulmonary fibrosis.¹ This variant is extremely rare in population databases, absent from gnomAD v2.1 and gnomAD-Canada, and present at an allele frequency of 6.3e-7 (1/1,586,736 alleles, 0 homozygotes) in gnomAD v4.1, satisfying PM2 at supporting strength.² Multiple lines of computational evidence suggest this variant is tolerated: BayesDel score is -0.237 (benign range), REVEL score is 0.296 (below the 0.5 pathogenicity threshold), and SpliceAI predicts no splicing impact (max delta = 0.01), collectively satisfying BP4 at supporting strength.³ No functional studies, case-control data, segregation analysis, or de novo observations were identified for this variant. ClinVar reports two clinical laboratory submissions, both classifying the variant as Uncertain significance. All reviewed publications discuss TERT at the gene level and do not mention this specific variant.⁴ Under the generic ACMG/AMP 2015 classification framework, the variant NM_198253.2:c.875C>T (p.Thr292Met) is classified as a Variant of Uncertain Significance (VUS), with balanced pathogenic (PM2_supporting) and benign (BP4_supporting) evidence. Additional evidence such as functional characterization, segregation data, or case-control studies would be needed to reclassify this variant.⁵