The PIK3CA c.1132T>C (p.Cys378Arg) variant has been reported in ClinVar with an overall Pathogenic classification, and curated somatic oncology resources also list this variant in cancer-associated context.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, including 0/1519490 alleles and 0 homozygotes in gnomAD v4.1, which supports rarity in population controls.² Curated functional literature links and a published PIK3CA study support a gain-of-function disease mechanism for mutant PIK3CA, but variant-specific assay evidence meeting Brain Malformations VCEP PS3 requirements was not established for p.Cys378Arg.³ The variant lies in a Brain Malformations VCEP-approved PIK3CA functional domain, a different missense change at the same residue has been reported as pathogenic, and SpliceAI predicts no splice effect; REVEL and BayesDel scores are also elevated, although PP3 is not applied by this VCEP for gain-of-function missense variants.⁴