NM_000489.5:c.3334A>G (p.Thr1112Ala) is a missense variant in ATRX, a chromatin remodeler gene associated with ATR-X syndrome and cancer predisposition. ATRX loss of function is an established germline disease mechanism.¹ This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada v1.0 (PM2). It is also absent from ClinVar.² Multiple in silico predictors suggest no damaging effect: BayesDel score is -0.527 (benign prediction) and SpliceAI predicts no splicing impact with a maximum delta score of 0.01 (BP4). REVEL score is not available.³ The variant has been reported in COSMIC (COSV64880047) with two somatic occurrences. No variant-specific functional studies, de novo reports, segregation data, or case-control evidence were identified. No functional data exist for this variant or a systematically characterized range that includes p.Thr1112. OncoKB classifies this variant as 'Unknown Oncogenic Effect.' No publications mention this exact variant.⁴ Applying generic ACMG/AMP 2015 combination rules: met criteria include PM2 (moderate) and BP4 (supporting benign). The evidence is conflicting with limited overall weight. No pathogenic criteria beyond PM2 are met, and BP4 provides supporting benign evidence. The variant is best classified as a Variant of Uncertain Significance.⁵