Is SCN10A p.Pro320Ser (c.958C>T) pathogenic?

SCN10A p.Pro320Ser (c.958C>T) is classified Uncertain significance in SCN10A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-02). AlphaMissense: ambiguous (0.4716); Very rare (popmax 8.52e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SCN10A p.Pro320Ser (c.958C>T)?

SCN10A p.Pro320Ser (c.958C>T) is associated with Cardiovascular phenotype, Brugada syndrome (ClinVar).

How common is SCN10A p.Pro320Ser (c.958C>T) in the general population?

SCN10A p.Pro320Ser (c.958C>T) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about SCN10A p.Pro320Ser (c.958C>T)?

AlphaMissense predicts ambiguous (score 0.4716) — an in-silico prediction, not a clinical call.

SCN10A p.Pro320Ser

c.958C>T · rs2470793382 · VCV2315844

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4716	ambiguous
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -11.13	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 97 kb · p 0.068 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.52e-05% European (non-Finnish) · 1/1,174,134 alleles

Overall 6.25e-05% 1/1,600,472 alleles · very rare exomes 1/1,448,214 · genomes 0/152,258 · 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: SCN10A
Protein: p.Pro320Ser
Coding: c.958C>T
MANE Select: NM_006514
dbSNP: rs2470793382
Type: single nucleotide variant
Location: chr3:38757152 (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

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-pro320ser (accessed [today's date]).

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