NM_007194.4:c.1604G>A (p.Arg535His) is a missense variant in CHEK2 located in the C-terminal region of the protein, outside the kinase and FHA domains.¹ Multiple independent computational predictors (REVEL 0.046, BayesDel -0.342, SpliceAI delta 0.00, SIFT Tolerated, Align GVGD C0, MutationTaster Polymorphism) converge on a benign interpretation, satisfying BP4 at supporting benign strength.² Direct functional assessment in a yeast-based assay (Delimitsou et al. 2019, PMID:30851065) characterized this variant as benign (wild-type-like function), consistent with the computational predictions.³ The variant is present in gnomAD population databases (v2.1: 63/264,906 alleles, AF=0.024%, grpmax FAF=0.16%, 1 homozygote; v4.1: 146/1,594,044 alleles, AF=0.0092%, grpmax FAF=0.11%, 2 homozygotes) with highest frequency in the South Asian subpopulation (0.20% v2.1).⁴ In ClinVar (VariationID 128067), this variant has received a mixed classification: Likely benign by 8 clinical laboratories, Uncertain significance by 6, and Benign by 1. Review status is single-submitter (1-star) rather than expert panel.⁵ No pathogenic ACMG/AMP criteria are met. No benign criteria are met beyond BP4 (supporting benign). The evidence is insufficient for a definitive benign classification; the variant remains a variant of uncertain significance (VUS), leaning benign based on computational and functional data.