NM_000465.4:c.1217G>A (p.Arg406Gln) is a missense variant in BARD1 exon 4. This variant is present at very low frequency in population databases: gnomAD v2.1 allele frequency 0.006% (17/282,356 alleles, 0 homozygotes) and gnomAD v4.1 allele frequency 0.002% (39/1,613,954 alleles, 1 homozygote), meeting PM2 (supporting).¹ Multiple lines of computational evidence predict a benign effect: REVEL score 0.117, BayesDel score -0.406678, and SpliceAI max delta 0.05, meeting BP4 (supporting).² Functional studies show conflicting results: p.R406Q is fully functional in homology-directed repair (149% of wild-type activity; PMID:26350354) but shows partially impaired apoptosis in patient-derived lymphoblastoid cells (TUNEL and Annexin V assays; PMID:31371347). Neither PS3 nor BS3 is met due to inconsistent evidence across assay types.³ This variant has been reported in two unrelated patients with early-onset colorectal cancer (ages 24 and 37; PMID:31371347), but colorectal cancer is not the classic BARD1-associated phenotype (hereditary breast and ovarian cancer).⁴ In ClinVar (Variation ID 127713), this variant is classified as Uncertain Significance by 8 clinical laboratories and Likely Benign by 1 laboratory, with no expert panel review available.⁵ No de novo, segregation, or case-control data are available. No pathogenic missense variant at the same residue has been identified (PM5 not met).