SCN3A p.Arg274=
c.820A>C · rs1274514552 · VCV1610172
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
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 1.5 | GERP -1.4, phastCons 1 |
| Overall | ||
| CADD | 9.134 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,024 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,038 alleles · very rare
exomes 1/1,461,864 · genomes 1/152,174 · joint denominator
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.Arg274=
- Coding
- c.820A>C
- MANE Select
- NM_006922
- dbSNP
- rs1274514552
- Type
- single nucleotide variant
- Location
- chr2:165162703 (GRCh38)
- Gene constraint
- LOEUF 0.348 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.76 · 2 PDB
- Residue 274
- an α-helix
Similar variants
- 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
- SCN3A p.Arg1621Gln Pathogenic/Likely pathogenic ★★ 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-arg274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown