NM_000051.4:c.7875T>G (p.Asp2625Glu) is a missense variant in exon 53 of ATM, observed at extremely low frequency in gnomAD v4.1 (AF = 6.82 × 10⁻⁶, 11/1,613,262 alleles), meeting PM2_Supporting.¹ In silico predictions are inconclusive: REVEL score (0.373) falls between the VCEP PP3 threshold (>0.7333) and BP4 threshold (≤0.249), and SpliceAI predicts no splicing impact (max delta = 0.07).² The variant is classified as 'Functional' (High confidence) in the ATM SNV combined-score table (PMID 40580951), reflecting in silico composite prediction rather than experimental functional data; no variant-specific functional assays are available.³ ClinVar reports this variant as Pathogenic (1 submitter, criteria provided, single submitter); however, the VCEP does not use PP5/BP6, and no independent case-level or functional evidence corroborates this classification.⁴ With only PM2_Supporting met and no other criteria satisfied, this variant does not reach a Likely Pathogenic or Likely Benign classification under the ACMG/AMP combination rules and is classified as a Variant of Uncertain Significance.⁵