SCN8A p.Lys159=
c.477G>A · rs781190497 · VCV1743035
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000343%, nfe)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.22 | donor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 15.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000343%
European (non-Finnish) · 4/1,166,414 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.00025%
4/1,598,692 alleles · very rare
exomes 2/1,446,514 · genomes 2/152,178 · 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
- SCN8A
- Protein
- p.Lys159=
- Coding
- c.477G>A
- MANE Select
- NM_001330260
- dbSNP
- rs781190497
- Type
- single nucleotide variant
- Location
- chr12:51686449 (GRCh38)
- Gene constraint
- LOEUF 0.189 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.90 · 7 PDB
- Residue 159
- an α-helix
Similar variants
- SCN8A p.Lys159Asn 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
- SCN8A p.Ser845Phe 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-lys159 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown