SCN8A p.Asp522=
c.1566T>C · rs768201816 · VCV1556282
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00448%, sas)
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 -4.3 | GERP -3.7 |
| Overall | ||
| CADD | 3.567 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00448%
South Asian · 4/89,316 alleles
Filtering AF
0.00335%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00303%
Overall
0.00342%
55/1,607,054 alleles · very rare
exomes 54/1,454,860 · genomes 1/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00448% | 22,329 |
| European (non-Finnish) | 0.00433% | 23,079 |
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.Asp522=
- Coding
- c.1566T>C
- MANE Select
- NM_001330260
- dbSNP
- rs768201816
- Type
- single nucleotide variant
- Location
- chr12:51706646 (GRCh38)
- Gene constraint
- LOEUF 0.189 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.90 · 7 PDB
- Residue 522
- 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-asp522 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown