NM_006218.4:c.2850A>G (p.Glu950=) is a synonymous variant in PIK3CA exon 20. The ClinGen Brain Malformations VCEP (v1.1) framework was applied for criterion adjudication.¹ The variant falls within the C-terminal kinase domain (AA 797-1068), a Table 4 critical functional domain for PIK3CA per the VCEP specification, meeting PM1 at Supporting strength.² The variant is extremely rare in population databases: gnomAD v2.1 AF=0.00080% (2/248,508 alleles), gnomAD v4.1 AF=0.00006% (1/1,611,758 alleles), with zero homozygotes. PM2 is met at Supporting strength under VCEP rules.³ PVS1, PS1, PM5, PM6, PP1, PP2, PP3, PP4, PP5, BS4, BP1, BP6, and BP3 are not applicable under the VCEP framework or due to the synonymous nature of the variant.⁴ SpliceAI predicts no significant splicing impact (max delta=0.05), but BP4 requires two of three tools (varSEAK, SpliceAI, MaxEntScan) per VCEP specifications; only SpliceAI is available. BP7 requires a PhyloP score <0.1, which is not available. Both BP4 and BP7 remain not assessed.⁵ No functional studies, de novo reports, case observations, or segregation data were identified for this synonymous variant. PS2, PS3, PS4, BS2, BS3, BP2, and BP5 are not met.⁶ With PM1_Supporting (+1) and PM2_Supporting (+1), the total points sum to +2. Per the VCEP Tavtigian point-combination framework (Pathogenic ≥10, Likely Pathogenic 6-9, VUS 0-5, Likely Benign -6 to -1, Benign <-6), a score of +2 falls within the VUS (0-5) range.⁷