SCN2A p.Ile1663Thr
c.4988T>C · rs2105402379 · VCV1342668
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9243 | likely pathogenic |
|---|---|---|
| REVEL | 0.967 | strongly pathogenic-leaning |
| SaProt | LLR -15.43 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Regional constraint | o/e 0.06 | constrained · MANE · 148 bp · p 2.7e-14 · regional, not allelic |
| Overall | ||
| CADD | 23.1 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SCN2A
- Protein
- p.Ile1663Thr
- Coding
- c.4988T>C
- MANE Select
- NM_001040142
- dbSNP
- rs2105402379
- Type
- single nucleotide variant
- Location
- chr2:165388794 (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.Ile1663Leu Uncertain significance ⚠ same residue
- SCN2A p.Ile1663fs Likely pathogenic ★ same residue
- SCN2A p.Ala1773Thr Pathogenic ★★★ same type
- SCN2A p.Arg220Gly Likely pathogenic ★★★ same type
- SCN2A p.Arg853Gln Pathogenic ★★★ same type
- SCN2A p.Gly899Asp Likely pathogenic ★★★ same type
- SCN2A p.Leu1611Pro Pathogenic ★★★ same type
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-ile1663thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown