Sturge–Weber syndrome (SWS) is a neurocutaneous disorder characterized by capillary malformation (port-wine stains), and choroidal and leptomeningeal vascular malformations. Previously, the recurrent somatic mutation c. 548G> A (p. R183Q) in the G-α q gene (GNAQ) was identified as causative in SWS and non-syndromic port-wine stain patients using whole-genome sequencing. In this study, we investigated somatic mutations in GNAQ by next-generation sequencing. We first performed targeted amplicon sequencing of 15 blood–brain-paired samples in sporadic SWS and identified the recurrent somatic c. 548G> A mutation in 80% of patients (12 of 15). The percentage of mutant alleles in brain tissues of these 12 patients ranged from 3.6 to 8.9%. We found no other somatic mutations in any of the seven GNAQ exons in the remaining three patients without c. 548G> A. These findings suggest that the recurrent somatic GNAQ mutation c. 548G> A is the major determinant genetic factor for SWS and imply that other mutated candidate gene (s) may exist in SWS.