The PIK3CA c.335T>C (p.Ile112Thr, p.I112T) variant has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1, supporting PM2_Supporting under the Brain Malformations VCEP rule for variants observed in no more than 1 person.² The p.Ile112Thr change affects residue 112, which is outside the PIK3CA Table 4 approved kinase-domain intervals of amino acids 322-483 and 797-1068, so PM1 is not met.³ Computational data show no predicted splice impact by SpliceAI (max delta score 0.00), with REVEL 0.39 and BayesDel 0.238394, but under this VCEP PP3 is not applicable and BP4 is restricted to synonymous, intronic, or UTR variants.⁴