NM_002392.5:c.500G>A (NP_002383.2:p.Arg167Lys) is a missense variant in MDM2 that is absent from all gnomAD population databases (v2.1, v4.1, and gnomAD-Canada), meeting PM2 at supporting level.¹ Multiple in silico tools uniformly predict a tolerated or benign effect: REVEL score 0.144, BayesDel score -0.333371, and SpliceAI max delta 0.00, meeting BP4 at supporting benign level.² The variant is absent from ClinVar, COSMIC, and the published literature. No functional studies, segregation data, de novo reports, or case-control data are available. No CSPEC/VCEP framework exists for MDM2.³ With PM2 (supporting pathogenic) and BP4 (supporting benign) as the only met criteria and all other criteria not assessed, the evidence is insufficient for classification. The variant is classified as a Variant of Uncertain Significance (VUS) per generic ACMG/AMP 2015 criteria.⁴