NM_012433.3:c.2352G>A (p.Met784Ile) is a missense variant in SF3B1, a gene encoding a core spliceosome component associated with both somatic malignancy and constitutional neurodevelopmental disorders. The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (allele frequency = 0.0), meeting PM2 at moderate strength.¹ Multiple in silico predictors suggest no significant impact: BayesDel score is 0.179 (benign range) and SpliceAI predicts no splicing alteration (max delta = 0.02), meeting BP4 at supporting benign strength. REVEL score of 0.538 is intermediate.² The variant is absent from ClinVar and has not been reported in the published literature as a germline variant. COSMIC records one somatic occurrence (COSV106472208) without functional characterization.³ No variant-specific functional studies (PS3), de novo observations (PS2/PM6), co-segregation data (PP1), or case-control data (PS4) are available. Computational evidence is equivocal (PP3 not met). No pathogenic comparator at the same residue exists (PM5 not met). The variant does not lie in a statistically significant hotspot (cancerhotspots.org) and position 784 is not a recognized recurrent mutation site (PM1 not met). SF3B1 germline disease involves both missense and loss-of-function variants (PMID:41577671), so BP1 does not apply. With one moderate pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is insufficient for classification. The variant remains a Variant of Uncertain Significance (VUS) under ACMG/AMP 2015 generic rules.⁴