Is SCN10A p.Pro71= (c.213A>G) pathogenic?

SCN10A p.Pro71= (c.213A>G) is classified Likely benign in SCN10A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-25). Ultra-rare (popmax 0.0165%, sas); Associated with Brugada syndrome.

What condition is associated with SCN10A p.Pro71= (c.213A>G)?

SCN10A p.Pro71= (c.213A>G) is associated with Brugada syndrome (ClinVar).

How common is SCN10A p.Pro71= (c.213A>G) in the general population?

SCN10A p.Pro71= (c.213A>G) is ultra-rare (popmax 0.0165%, sas) (gnomAD).

How is Brugada syndrome inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SCN10A p.Pro71=

c.213A>G · rs533136525 · VCV1115101

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, sas)

Conditions

Brugada syndrome

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 -13	GERP -4.5
Overall
CADD	0.246	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% South Asian · 15/91,064 alleles

Filtering AF 0.0101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00136% 22/1,613,940 alleles · ultra-rare exomes 20/1,461,764 · genomes 2/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0165%	6,071
East Asian	0.0111%	8,971
Remaining individualsnot grpmax-eligible	0.0032%	31,249

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.Pro71=
Coding: c.213A>G
MANE Select: NM_006514
dbSNP: rs533136525
Type: single nucleotide variant
Location: chr3:38793798 (GRCh38)
Gene constraint: LOEUF 1.058 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.06 · 8 PDB

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

Disease context

Brugada syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Brugada syndrome (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SCN10A p.Pro71Leu Uncertain significance ★ ⚠ same residue
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

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-pro71 (accessed [today's date]).

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