SCN8A p.Pro512=
c.1536C>T · rs770320050 · VCV1124200
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
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 -4.9 | GERP -3.7 |
| Overall | ||
| CADD | 5.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,740 alleles
Filtering AF
0.00817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00635%
Overall
0.00124%
20/1,607,814 alleles · ultra-rare
exomes 12/1,455,734 · genomes 8/152,080 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,795 |
| East Asian | 0.00224% | 44,660 |
| South Asian | 0.00111% | 89,696 |
| European (non-Finnish) | 0.000595% | 168,132 |
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
- SCN8A
- Protein
- p.Pro512=
- Coding
- c.1536C>T
- MANE Select
- NM_001330260
- dbSNP
- rs770320050
- Type
- single nucleotide variant
- Location
- chr12:51706616 (GRCh38)
- Gene constraint
- LOEUF 0.189 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.90 · 7 PDB
- Residue 512
- the 'disordered' region
Similar variants
- SCN8A c.615-1G>A Pathogenic ★★★ same condition
- SCN8A p.Arg1872Gln Pathogenic ★★★ ⚠ same condition
- SCN8A p.Asn418Asp Likely pathogenic ★★★ same condition
- SCN8A p.Glu1218Lys Pathogenic ★★★ same condition
- SCN8A p.Ile1631Thr Likely pathogenic ★★★ same condition
- SCN8A p.Ser845Cys Likely pathogenic ★★★ ⚠ same condition
- SCN8A p.Ser845Phe Likely pathogenic ★★★ ⚠ same condition
- SCN8A p.Tyr401His 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/scn8a-p-pro512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown