NM_003925.3:c.1015G>A (p.Ala339Thr) is absent from all gnomAD population databases (v2.1, v4.1, Canada), meeting PM2 at supporting strength.¹ MBD4 germline disease is mediated by loss-of-function via truncating variants; this missense variant qualifies for BP1 (supporting benign) as missense variation is not the established pathogenic mechanism. Computational predictors are discordant: REVEL 0.302 (weakly pathogenic-leaning), BayesDel -0.489624 (benign-leaning), SpliceAI max delta 0.27 (intermediate). Neither PP3 nor BP4 is met.² No functional studies, no case-control data, no segregation data, no de novo observations, and no ClinVar entries exist for this variant. All other criteria are not met or not applicable.³ With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP1), the net evidence score is zero, consistent with a variant of uncertain significance (VUS) per ACMG/AMP 2015 generic classification rules.⁴