SCN2A p.Val261=
c.783G>C · rs1250340830 · VCV1118349
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
developmental and epileptic encephalopathy, 11
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.23 | GERP 0.16, phastCons 0.021 |
| Overall | ||
| CADD | 4.116 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,970 alleles
Overall
0.000658%
1/152,074 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- SCN2A
- Protein
- p.Val261=
- Coding
- c.783G>C
- MANE Select
- NM_001040142
- dbSNP
- rs1250340830
- Type
- single nucleotide variant
- Location
- chr2:165310408 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.28 · 5 PDB
- Residue 261
- a UniProt-annotated variant site (found in a patient with intractable epilepsy and severe mental decline; likely pathogenic; non-conducting; loss of voltage-gated sodium channel activity; dominant-negative); a UniProt-annotated variant site (found in a patient with schizofrenia; uncertain significance); a UniProt-annotated variant site (in bfis3; increased voltage-gated sodium channel activity; faster recovery from inactivation; gain of function); an α-helix
Similar variants
- SCN2A p.Val261Met Pathogenic ★★ same residue
- SCN2A p.Val261Leu Pathogenic ★ same residue
- SCN2A p.Ala1773Thr Pathogenic ★★★ same condition
- SCN2A p.Arg220Gly Likely pathogenic ★★★ same condition
- SCN2A p.Arg853Gln Pathogenic ★★★ same condition
- SCN2A p.Gly899Asp Likely pathogenic ★★★ same condition
- SCN2A p.Leu1611Pro Pathogenic ★★★ same condition
- SCN2A p.Leu886Ser Likely pathogenic ★★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/scn2a-p-val261 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown