SCN1A p.Pro76=
c.228C>G · rs1173774565 · VCV704519
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000763%, nfe)
Conditions
1
early-infantile DEE
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 -3.9 | GERP -5.4 |
| Overall | ||
| CADD | 1.073 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000763%
European (non-Finnish) · 9/1,179,992 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000558%
9/1,613,998 alleles · very rare
exomes 9/1,461,828 · genomes 0/152,170 · joint denominator
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
- SCN1A
- Protein
- p.Pro76=
- Coding
- c.228C>G
- MANE Select
- NM_001165963
- dbSNP
- rs1173774565
- Type
- single nucleotide variant
- Location
- chr2:166073394 (GRCh38)
- Gene constraint
- LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.97 · 1 PDB
Similar variants
- SCN1A p.Pro76Leu Likely pathogenic ★ same residue
- SCN1A p.Pro76Ser Likely pathogenic ★ same residue
- SCN1A p.Pro76Thr Pathogenic ★ same residue
- SCN1A p.Ala420Val Likely pathogenic ★★★ same condition
- SCN1A p.Arg1639Pro Pathogenic ★★★ same condition
- SCN1A p.Arg219Gly Likely pathogenic ★★★ same condition
- SCN1A p.Arg219Thr Likely pathogenic ★★★ same condition
- SCN1A p.Arg931His 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/scn1a-p-pro76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown