NM_000215.3:c.1531A>G (p.Met511Val) is a missense variant in exon 11 of JAK3 affecting the pseudokinase domain. This variant is extremely rare in population databases, with a popmax filtering allele frequency of 8.79e-06 in gnomAD v2.1 and 8.47e-06 in v4.1 (European non-Finnish), and zero homozygotes observed, meeting PM2_Supporting per SCID VCEP specifications (threshold <0.000115).¹ The variant is absent from ClinVar, COSMIC, and gnomAD-Canada.² No variant-specific functional evidence is available. The SCID VCEP-approved PS3_Supporting in vitro kinase assay (PMID:14615376) tested other JAK3 variants but not M511V. The related M511I variant has been characterized in a somatic T-ALL context (PMID:25193870) but these findings cannot be directly extrapolated to germline M511V in SCID.³ No de novo observations, segregation data, or patient phenotype information is available. PM1 does not apply because M511 is not one of the two specified JH2 domain residues (R651, C759).⁴ Based on SCID VCEP v2.3.0 criteria, the only applicable criterion met is PM2_Supporting. This is insufficient for classification as Likely Pathogenic or Pathogenic. The variant is classified as a Variant of Uncertain Significance (VUS).⁵