SCN5A p.Ser910=
c.2730G>A · rs377561353 · VCV922918
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0108%, afr)
Conditions
1
cardiac rhythm disease
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 -9.3 | GERP -6.5 |
| Overall | ||
| CADD | 0.615 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0108%
African / African-American · 8/73,884 alleles
Filtering AF
0.00534%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00385%
Overall
0.00149%
24/1,609,102 alleles · ultra-rare
exomes 17/1,461,112 · genomes 7/147,990 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0108% | 9,235 |
| East Asian | 0.00224% | 44,574 |
| European (non-Finnish) | 0.00119% | 84,162 |
| South Asian | 0.0011% | 90,776 |
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
- SCN5A
- Protein
- p.Ser910=
- Coding
- c.2730G>A
- MANE Select
- NM_000335
- dbSNP
- rs377561353
- Type
- single nucleotide variant
- Location
- chr3:38585748 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.02 · 16 PDB
- Residue 910
- a UniProt-annotated variant site (in brgda1); an α-helix
Similar variants
- SCN5A p.Ser910Leu Pathogenic/Likely pathogenic ★★ same residue
- SCN5A c.1338+2T>A Pathogenic/Likely pathogenic ★★ same condition
- SCN5A c.2263-2A>G Likely pathogenic ★★ same condition
- SCN5A c.3508+1G>T Likely pathogenic ★★ same condition
- SCN5A c.3837+1G>A Pathogenic ★★ same condition
- SCN5A c.4242+1G>C Pathogenic/Likely pathogenic ★★ same condition
- SCN5A c.611+1G>A Pathogenic ★★ same condition
- SCN5A c.934+1G>A 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/scn5a-p-ser910 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown