SMAD4 is tumor suppressor gene and it encodes an intracellular mediator in the transforming growth factor b (TGF b) signal transduction pathway. Somatic mutations in SMAD4 are exceedingly rare in glial neoplasms. SMAD4 I525V has been reported as a likely benign germline variant in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/41788/). These results should be interpreted in the clinical context.