NM_000051.4:c.4574T>C (p.Ile1525Thr) is a rare missense variant in ATM, present at extremely low frequency in gnomAD v4.1 (10/1,614,116 alleles; grpmax FAF = 1.425×10⁻⁵).¹ This variant has been reported in ClinVar as Uncertain Significance by 5 clinical laboratories (ClinVar ID 230535); no expert panel submission is available.² The VCEP HBOP v1.5.0 PVS1 criterion is not applicable because this is a missense variant, not a null variant.³ Multiple lines of in silico evidence support a benign impact: REVEL score 0.116 is below the VCEP BP4 threshold (≤0.249), SpliceAI predicts no splice impact (max delta 0.06), and BayesDel score is −0.336. BP4 (supporting benign) is met.⁴ No variant-specific functional studies, case-control data, segregation data, or pathogenic comparator at the same residue were identified in the literature. All other applicable VCEP criteria are not met.⁵ Based on the VCEP HBOP v1.5.0 framework, the only criterion met is BP4_Supporting (benign). No pathogenic criteria are met. With only one supporting benign criterion and no conflicting evidence, the variant does not reach a classification threshold under the ACMG/AMP combining rules and remains a Variant of Uncertain Significance.⁶