SCN8A p.Phe1447=
c.4341C>T · rs1298845619 · VCV2770681
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 1.9, phastCons 1 |
| Overall | ||
| CADD | 14.42 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,886 alleles
Overall
6.2e-05%
1/1,614,028 alleles · very rare
exomes 1/1,461,708 · genomes 0/152,320 · 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.Phe1447=
- Coding
- c.4341C>T
- MANE Select
- NM_001330260
- dbSNP
- rs1298845619
- Type
- single nucleotide variant
- Location
- chr12:51789340 (GRCh38)
- Gene constraint
- LOEUF 0.189 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.90 · 7 PDB
- Residue 1447
- an α-helix
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-phe1447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown