SCN2A p.Phe404fs
c.1208dup · VCV3381753
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
SCN2A-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 10 of 27 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- SCN2A
- Protein
- p.Phe404fs
- Coding
- c.1208dup
- MANE Select
- NM_001040142
- Type
- Duplication
- Location
- chr2:165313932 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.28 · 5 PDB
- Residue 404
- 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); an α-helix
Similar variants
- SCN2A p.Ser661fs Pathogenic ★★ same condition
- SCN2A p.Met381fs Likely pathogenic ★ same condition
- SCN2A p.Thr1623fs Likely pathogenic ★ same condition
- SCN2A p.Val256fs Likely pathogenic ★ same condition
- SCN2A p.Cys910fs Likely pathogenic same condition
- SCN2A p.Ala1773Thr Pathogenic ★★★ same condition
- SCN2A p.Ala1316Val Pathogenic/Likely pathogenic ★★ same condition
- SCN2A p.Ala1773Val Pathogenic/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-phe404fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown