SCN3A p.Asp45=
c.135T>C · rs768514926 · VCV412609
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -1.2 | GERP -5.7 |
| Overall | ||
| CADD | 2.849 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,056 alleles
Filtering AF
0.00582%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00223%
36/1,611,610 alleles · ultra-rare
exomes 33/1,461,442 · genomes 3/150,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,028 |
| Admixed American | 0.00334% | 29,958 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,229 |
| European (non-Finnish) | 0.00246% | 40,650 |
| African / African-American | 0.00134% | 74,632 |
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
- SCN3A
- Protein
- p.Asp45=
- Coding
- c.135T>C
- MANE Select
- NM_006922
- dbSNP
- rs768514926
- Type
- single nucleotide variant
- Location
- chr2:165176260 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 2 PDB
- Residue 45
- the 'disordered' region
Similar variants
- SCN3A p.Asp45Glu Uncertain significance ★★ ⚠ same residue
- SCN3A p.Ile875Thr Pathogenic ★★★ same type
- SCN3A p.Gly876Ser Uncertain significance ★★★ ⚠ same type
- SCN3A p.Asp1803Asn Benign ★★★ same type
- SCN3A p.Asp815Asn Benign ★★★ same type
- SCN3A p.Gly1862Cys Benign ★★★ same type
- SCN3A p.Gly900Ser Likely benign ★★★ same type
- SCN3A p.Val1084Ile 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/scn3a-p-asp45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown