NM_006218.4:c.1458C>T is a synonymous variant (p.Phe486=) in PIK3CA exon 9. Under the ClinGen Brain Malformations VCEP v1.1, PVS1, PP1, PP3, PP4, PP5, PM6, BS4, BP1, and BP6 are not applicable.¹ PS1, PS5, and PM5 are not applicable because the variant is synonymous and produces no amino acid change.² The variant is present in gnomAD v2.1 (2/249,396 alleles; 0.0008%) and v4.1 (19/1,613,762 alleles; 0.00118%), exceeding the VCEP PM2_Supporting threshold of ≤1 allele. The allele frequency does not reach BA1 (>0.0926%) or BS1 (>0.0185%) thresholds. Zero homozygotes are observed (BS2 not met).³ Residue 486 lies outside both PIK3CA critical functional domains defined by the VCEP Table 4 (AA 322-483 and AA 797-1068); PM1_Supporting is not met.⁴ No functional studies, de novo occurrences, brain malformation case reports, or co-segregation data were identified for this variant. ClinVar classifies it as Likely benign (3 clinical laboratories, single submitter, no expert panel review).⁵ BP4 and BP7 remain unassessed due to missing splicing prediction (varSEAK, MaxEntScan) and conservation (PhyloP) data. SpliceAI predicts no splice impact (max delta 0.01).⁶ No reviewable publications contained variant-specific evidence. All ClinVar-associated PMIDs are guideline or policy documents that do not mention NM_006218.4:c.1458C>T.