This variant is completely absent from population databases including gnomAD v2.1 (0/248,624 alleles) and gnomAD v4.1 (0/1,611,102 alleles), meeting PM2_Supporting per the Brain Malformations VCEP.¹ No other pathogenic or benign criteria are met under the Brain Malformations VCEP v1.1.0 framework. PVS1, PP3, PP4, PP5, BS4, PM6, BP1, BP4, BP6, BP7, and PP1 are explicitly not applicable per the VCEP. Most remaining criteria lack variant-specific evidence in the published literature.² OncoKB curates p.Arg38Cys as Likely Oncogenic with Likely Gain-of-function biological context; however, no variant-specific functional data was identified in the reviewed full-text publications, and the Brain Malformations VCEP PS3 criterion requires validated functional assays meeting specific quality metrics.³ This variant has been reported in ClinVar as Uncertain significance by two clinical laboratories (ClinVarID 376493). No de novo reports, segregation data, or brain malformation phenotype cases were identified.⁴ Variant has been observed in somatic cancers (COSMIC, n=39 occurrences) but this does not independently support germline brain malformation pathogenicity under the VCEP PS4 framework.