Is SCN4B p.Asp97= (c.291C>T) pathogenic?

SCN4B p.Asp97= (c.291C>T) is classified Likely benign in SCN4B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-17). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with SCN4B p.Asp97= (c.291C>T)?

SCN4B p.Asp97= (c.291C>T) is associated with Cardiovascular phenotype, long QT syndrome 10 (ClinVar).

How common is SCN4B p.Asp97= (c.291C>T) in the general population?

SCN4B p.Asp97= (c.291C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

SCN4B p.Asp97=

c.291C>T · rs919578520 · VCV1797678

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

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 -8.1	GERP -3.6
Overall
CADD	0.186	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,912 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00124% 20/1,614,008 alleles · very rare exomes 16/1,461,816 · genomes 4/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,456
East Asian	0.00223%	44,904
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)	0.00119%	84,284
South Asian	0.0011%	91,088

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.Asp97=
Coding: c.291C>T
MANE Select: NM_174934
dbSNP: rs919578520
Type: single nucleotide variant
Location: chr11:118144005 (GRCh38)
Gene constraint: LOEUF 1.324 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91 · 5 PDB
Residue 97: a β-strand; the ig-like c2-type domain

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-asp97 (accessed [today's date]).

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