The c.1259C>T variant in SCN1A is a missense variant predicted to cause substitution of alanine by valine at amino acid 420 (p.Ala420Val). The variant has been identified as a de novo occurrence with unconfirmed parental relationships in two individuals with a consistent phenotype in the published literature (PMIDs:35696452, 26096185) (PM6_Moderate), and in one individual with seizures and intellectual disability with unknown inheritance (PMID: 22944210) (PS4_Supporting). The variant is absent from the population database, gnomAD v4.0 (PM2_Supporting). A novel missense variant at the corresponding position in the paralogous gene, SCN8A (p.Ala408Thr), has been previously reported (PMID: 26993267), however, >1 novel variant in a paralogous gene is required for PM5 (not met). The computational predictor REVEL gives a score of 0.95, which is above the threshold of 0.773, evidence that correlates with a maximum strength of PP3_Moderate. In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal dominant SCN1A-related disorder based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: PM6_Moderate, PS4_Supporting, PM2_Supporting, PP3_Moderate. (version 1.0; July 23, 2024).