SCN5A p.Phe355=
c.1065C>T · rs45570333 · VCV139046
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00347%, nfe)
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 -3.1 | GERP -0.74 |
| Overall | ||
| CADD | 7.362 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00347%
European (non-Finnish) · 41/1,179,894 alleles
Filtering AF
0.00259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00233%
Overall
0.00273%
44/1,613,824 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00347% | 28,778 |
| Admixed American | 0.00167% | 60,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,458 |
| African / African-American | 0.00133% | 74,942 |
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.Phe355=
- Coding
- c.1065C>T
- MANE Select
- NM_000335
- dbSNP
- rs45570333
- Type
- single nucleotide variant
- Location
- chr3:38606744 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.02 · 16 PDB
- Residue 355
- a β-strand
Similar variants
- 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
- SCN5A p.Ala735Val Pathogenic/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/scn5a-p-phe355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown