SCN8A p.Arg573=
c.1717C>A · rs370074236 · VCV391292
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
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 1.1 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 12.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,876 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00211%
34/1,612,720 alleles · very rare
exomes 30/1,460,510 · genomes 4/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,938 |
| European (non-Finnish) | 0.00263% | 38,046 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,412 |
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.Arg573=
- Coding
- c.1717C>A
- MANE Select
- NM_001330260
- dbSNP
- rs370074236
- Type
- single nucleotide variant
- Location
- chr12:51721627 (GRCh38)
- Gene constraint
- LOEUF 0.189 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.90 · 7 PDB
- Residue 573
- the 'disordered' region
Similar variants
- SCN8A p.Arg573Trp Uncertain significance ★ ⚠ same residue
- SCN8A p.Arg573Leu Uncertain significance ★ ⚠ same residue
- 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
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-arg573 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown