NM_002878.3:c.422T>C (p.Leu141Pro) is a missense variant in RAD51D, a moderate-penetrance ovarian cancer predisposition gene where loss-of-function is the established disease mechanism.¹ This variant is present at extremely low frequency in population databases: gnomAD v2.1 AF=0.0004% (1/251,470 alleles) and gnomAD v4.1 AF=0.0011% (18/1,614,128 alleles), and is absent from gnomAD-Canada. PM2 (supporting) is met.² ClinVar reports this variant as Uncertain significance by seven clinical laboratories with review status 'criteria provided, single submitter.' No expert panel pathogenic or benign classification exists.³ In silico predictions are mixed: REVEL score 0.44 (indeterminate), BayesDel score 0.07 (benign), and SpliceAI max delta 0.04 (no splice impact). These do not meet PP3 or BP4 thresholds.⁴ No functional studies, case-control data, cosegregation data, or de novo observations are available for this variant. PS3, PS4, PP1, PS2, and PM6 remain unassessed. No same-residue pathogenic comparator exists at Leu141, precluding PS1 and PM5 application.⁵ RAD51D has both established pathogenic truncating and missense variants; BP1 is not met because missense variants cannot be presumed benign in this gene.⁶ Overall, this variant meets only PM2 (supporting). All other applicable criteria are either not met or cannot be assessed due to insufficient evidence. The variant remains of uncertain significance.