NM_000051.4:c.9139C>T (p.Arg3047Ter) is a nonsense variant in exon 63 of ATM, creating a premature termination codon at the most C-terminal residue considered pathogenic by the HBOP VCEP (p.Arg3047). PVS1 is applied at very strong strength under the ATM PVS1 Decision Tree as a null variant in a gene where loss of function is a known disease mechanism.¹ This variant has been reported in ClinVar as Pathogenic by the ClinGen HBOP VCEP expert panel and by 18 clinical laboratories (ClinVar Variation ID: 3029).² The variant is present in gnomAD v4.1 at an extremely low frequency (AF=1.61×10⁻⁵, 26/1,613,988 alleles; no homozygotes), consistent with a rare disease-causing variant. It is also present in gnomAD v2.1 at similar frequency (AF=1.77×10⁻⁵, 5/282,840 alleles).³ Functional characterization by Guo et al. (2010, PMID 21150274) demonstrates that the R3047X mutant protein is expressed but specifically deficient in oxidation-dependent ATM activation while retaining MRN/DNA-dependent activation. Cells from an A-T patient with this variant showed moderate radiosensitivity, consistent with preserved DNA damage response but lost oxidative stress signaling.⁴ Chessa et al. (2009, PMID 19691550) identified c.9139C>T in two Italian A-T families from Central Italy, confirming observation of this variant in individuals with classical ataxia-telangiectasia.⁵ No VCEP-approved functional assay data, case-control studies, or detailed co-segregation data were available from the reviewed sources. Additional supporting evidence may exist in curated databases not accessible in this assessment. The ClinGen expert panel classification of Pathogenic likely incorporates proband data and/or additional supporting criteria not available here.