SCN7A p.Phe644=
c.1932C>T · rs72886662 · VCV731513
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.138%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.97 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -4.8 |
| Overall | ||
| CADD | 1.436 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.138%
European (non-Finnish) · 1,629/1,179,806 alleles
Filtering AF
0.132%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.13%
Overall
0.109%
1,757/1,613,840 alleles · rare
exomes 1,649/1,461,584 · genomes 108/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.138% | 724 |
| Remaining individualsnot grpmax-eligible | 0.102% | 976 |
| Admixed American | 0.0433% | 2,307 |
| African / African-American | 0.0307% | 3,262 |
| Middle Eastern | 0.0165% | 6,060 |
| Finnishnot grpmax-eligible | 0.0156% | 6,401 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
| East Asian | 0.00223% | 44,870 |
| South Asian | 0.0011% | 91,068 |
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
- SCN7A
- Protein
- p.Phe644=
- Coding
- c.1932C>T
- MANE Select
- NM_002976
- dbSNP
- rs72886662
- Type
- single nucleotide variant
- Location
- chr2:166441621 (GRCh38)
- Gene constraint
- LOEUF 1.124 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.18 · 2 PDB
- Residue 644
- an α-helix
Similar variants
- SCN7A p.Val187Ile Uncertain significance ★★ ⚠ same type
- SCN7A c.3028-9A>T Benign ★★ same type
- SCN7A p.Ala1282Val Benign ★★ same type
- SCN7A p.Ala1313= Benign/Likely benign ★★ same type
- SCN7A p.Ala456Gly Likely benign ★★ same type
- SCN7A p.Ala818Ser Likely benign ★★ same type
- SCN7A p.Arg1106Gln Likely benign ★★ same type
- SCN7A p.Arg1516Lys Likely benign ★★ same type
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/scn7a-p-phe644 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown