SCN1A p.Pro752=
c.2256A>G · VCV4770100
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
early-infantile DEE
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -2.4, phastCons 0.99 |
| Overall | ||
| CADD | 9.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
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
- SCN1A
- Protein
- p.Pro752=
- Coding
- c.2256A>G
- MANE Select
- NM_001165963
- Type
- single nucleotide variant
- Location
- chr2:166041390 (GRCh38)
- Gene constraint
- LOEUF 0.098 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.97 · 1 PDB
- Residue 752
- a UniProt-annotated variant site (in drvt); an α-helix
Similar variants
- SCN1A p.Pro752fs Pathogenic ★ same residue
- SCN1A p.Pro752Leu Uncertain significance ★ ⚠ 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
- SCN1A p.Pro768Leu 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/scn1a-p-pro752 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown