SCN2A p.Ile1663fs
c.4989del · rs1702009872 · VCV983149
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 | escapes | premature termination codon in the last exon (27 of 27) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- SCN2A
- Protein
- p.Ile1663fs
- Coding
- c.4989del
- MANE Select
- NM_001040142
- dbSNP
- rs1702009872
- Type
- Deletion
- Location
- chr2:165388795 (GRCh38)
- Gene constraint
- LOEUF 0.161 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.28 · 5 PDB
- Residue 1663
- 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 (found in a patient with autism spectrum disorder; likely pathogenic); a UniProt-annotated variant site (found in a patient with autism spectrum disorder; likely pathogenic; loss of voltage-gated sodium channel activity; non-conducting); a UniProt-annotated variant site (in dee11); an α-helix
Similar variants
- SCN2A p.Ile1663= Benign/Likely benign ★★ same residue
- SCN2A p.Leu577fs Pathogenic ★★ same condition
- SCN2A p.Phe1661fs Pathogenic/Likely pathogenic ★★ same condition
- SCN2A p.Ser484fs Pathogenic ★★ same condition
- SCN2A c.605+4_605+7del Uncertain significance ★★ same condition
- SCN2A p.Glu1956_Asn1957del Uncertain significance ★★ same condition
- SCN2A p.Lys1946del Uncertain significance ★★ same condition
- SCN2A c.1034+1del 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-ile1663fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown