NM_000051.4:c.7486G>C (p.Gly2496Arg) is a missense variant in ATM exon 50. This variant is extremely rare in population databases: present in gnomAD v4.1 at an allele frequency of 0.00037% (6/1,614,098 alleles, 0 homozygotes), meeting the VCEP threshold for PM2_Supporting.¹ Multiple lines of computational evidence suggest a benign effect: REVEL score is 0.189 (meeting the VCEP BP4 threshold of ≤0.249), BayesDel score is negative (-0.183511), and SpliceAI predicts no splicing impact (max delta 0.04). BP4_Supporting is applied.² The ATM VCEP supplementary in silico meta-predictor (Suppl_TableS1, PMID:40580951) classifies this variant as 'Functional' with High confidence (Combined score 0.962), consistent with the benign computational evidence.³ This variant has been reported in ClinVar as Uncertain significance by three clinical laboratories (Variation ID: 569749).⁴ PVS1, PS1, PM1, PM5, PM6, PS2, PP1, PP2, PP4, PP5, BS2, BS4, BP1, BP5, BP6, and BP7 are not applicable per ATM VCEP v1.5.0 specifications.⁵ No variant-specific experimental functional studies, case-control data, or segregation data were identified for this variant. Applying the ATM VCEP v1.5.0 classification framework: PM2_Supporting (1 pathogenic supporting point) and BP4_Supporting (1 benign supporting point). Per the generic ACMG/AMP 2015 combination rules (Rule 31), one pathogenic supporting criterion and one benign supporting criterion result in conflicting evidence, yielding an overall classification of Uncertain Significance.⁶