SCN3A p.Ser554=
c.1662C>T · rs760885665 · VCV1161891
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, sas)
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 -5.2, phastCons 1 |
| Overall | ||
| CADD | 3.45 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
South Asian · 15/91,070 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00688%
111/1,613,830 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0165% | 6,071 |
| European (non-Finnish) | 0.00797% | 12,552 |
| East Asian | 0.00223% | 44,876 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
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.Ser554=
- Coding
- c.1662C>T
- MANE Select
- NM_006922
- dbSNP
- rs760885665
- Type
- single nucleotide variant
- Location
- chr2:165146748 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 2 PDB
Similar variants
- SCN3A p.Ser554Phe 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-ser554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown