Is SCN10A p.Ile1237= (c.3711T>A) pathogenic?

SCN10A p.Ile1237= (c.3711T>A) is classified Likely benign in SCN10A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Very rare (popmax 0.0061%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SCN10A p.Ile1237= (c.3711T>A)?

SCN10A p.Ile1237= (c.3711T>A) is associated with Cardiovascular phenotype, Brugada syndrome (ClinVar).

How common is SCN10A p.Ile1237= (c.3711T>A) in the general population?

SCN10A p.Ile1237= (c.3711T>A) is very rare (popmax 0.0061%, nfe) (gnomAD).

SCN10A p.Ile1237=

c.3711T>A · rs148339462 · VCV463251

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0061%, nfe)

Conditions

Cardiovascular phenotype

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 0.31	GERP -4.2, phastCons 0.054
Overall
CADD	6.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0061% European (non-Finnish) · 72/1,180,032 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00465% 75/1,614,048 alleles · very rare exomes 72/1,461,866 · genomes 3/152,182 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0061%	16,389
Remaining individualsnot grpmax-eligible	0.0048%	20,829

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: SCN10A
Protein: p.Ile1237=
Coding: c.3711T>A
MANE Select: NM_006514
dbSNP: rs148339462
Type: single nucleotide variant
Location: chr3:38714051 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 8 PDB
Residue 1237: an α-helix

Full SCN10A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Brugada syndrome

Similar variants

SCN10A c.1093-3C>A Uncertain significance ★★ same condition
SCN10A c.2106+1G>A Uncertain significance ★★ same condition
SCN10A c.270+2T>C Uncertain significance ★★ same condition
SCN10A c.271-2A>G Uncertain significance ★★ same condition
SCN10A c.3804+1G>A Uncertain significance ★★ same condition
SCN10A c.3804+5G>C Uncertain significance ★★ same condition
SCN10A c.4089+1G>A Uncertain significance ★★ same condition
SCN10A c.4144-3C>A Uncertain significance ★★ 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/scn10a-p-ile1237 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown