NM_005475.2:c.419G>C (p.Arg140Pro) is a missense variant in SH2B3 exon 2 that is absent from ClinVar and present at extremely low frequency in gnomAD v4.1 (3/1,472,034 alleles; AF=0.00020%).¹ PM2 (supporting) is met: the variant is at extremely low population frequency, well below the 0.1% threshold.² BP4 (supporting benign) is met: concordant in silico predictions from REVEL (0.165) and BayesDel (-0.347) indicate a benign effect, and SpliceAI predicts no splice alteration (max delta 0.00).³ PVS1 is not applicable as this is a missense variant that does not fall into any null-variant category per ClinGen SVI PVS1 recommendations.⁴ No pathogenic or benign criteria beyond PM2 and BP4 are met. No variant-specific functional data, clinical observations, de novo events, segregation data, or literature reports exist for this variant. With one supporting pathogenic criterion (PM2) and one supporting benign criterion (BP4), the evidence is balanced with a slight lean toward uncertain significance given the absence of any functional or clinical data.⁵