Is SCN4B p.Pro11= (c.33G>A) pathogenic?

SCN4B p.Pro11= (c.33G>A) is classified Likely benign in SCN4B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). Very rare (popmax 0.000339%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with SCN4B p.Pro11= (c.33G>A)?

SCN4B p.Pro11= (c.33G>A) is associated with Cardiovascular phenotype, long QT syndrome 10 (ClinVar).

How common is SCN4B p.Pro11= (c.33G>A) in the general population?

SCN4B p.Pro11= (c.33G>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

SCN4B p.Pro11=

c.33G>A · rs755861941 · VCV1580191

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000339%, 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 1.6	GERP 0.78, phastCons 0.9
Overall
CADD	14.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,004 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,142 alleles · very rare exomes 4/1,459,816 · genomes 0/152,326 · 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: SCN4B
Protein: p.Pro11=
Coding: c.33G>A
MANE Select: NM_174934
dbSNP: rs755861941
Type: single nucleotide variant
Location: chr11:118152641 (GRCh38)
Gene constraint: LOEUF 1.324 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB

Full SCN4B 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: long QT syndrome 10

Similar variants

SCN4B c.234+1G>A Uncertain significance ★★ same condition
SCN4B c.463+3A>T Uncertain significance ★★ same condition
SCN4B c.594-2A>G Uncertain significance ★★ same condition
SCN4B c.61+1G>A Uncertain significance ★★ same condition
SCN4B c.62-1G>A Uncertain significance ★★ same condition
SCN4B c.*961A>G Uncertain significance ★★ same condition
SCN4B p.Ala12Thr Uncertain significance ★★ ⚠ same condition
SCN4B p.Arg195Trp 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/scn4b-p-pro11 (accessed [today's date]).

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