Is DSP p.Ala2294Gly (c.6881C>G) pathogenic?

DSP p.Ala2294Gly (c.6881C>G) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 21 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.8815); Rare (popmax 0.213%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Ala2294Gly (c.6881C>G)?

DSP p.Ala2294Gly (c.6881C>G) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Ala2294Gly (c.6881C>G) in the general population?

DSP p.Ala2294Gly (c.6881C>G) is rare (popmax 0.213%, amr) (gnomAD).

What do computational predictors say about DSP p.Ala2294Gly (c.6881C>G)?

AlphaMissense predicts likely pathogenic (score 0.8815) — an in-silico prediction, not a clinical call.

DSP p.Ala2294Gly

c.6881C>G · rs147000526 · VCV44943

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 21 submitters

AlphaMissense

likely pathogenic

0.8815 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.213%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8815	likely pathogenic
REVEL	0.72	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 696 bp · p 9.7e-06 · regional, not allelic
Overall
CADD	26.2	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 0.213% Admixed American · 128/60,028 alleles

Filtering AF 0.183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.172%

Overall 0.0794% 1,282/1,614,152 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.213%	469
Remaining individualsnot grpmax-eligible	0.096%	1,042
European (non-Finnish)	0.088%	1,137
Finnishnot grpmax-eligible	0.0312%	3,201
South Asian	0.0242%	4,139
African / African-American	0.0187%	5,359

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: DSP
Protein: p.Ala2294Gly
Coding: c.6881C>G
MANE Select: NM_004415
dbSNP: rs147000526
Type: single nucleotide variant
Location: chr6:7584143 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2294: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); a UniProt-annotated variant site (in ebla; uncertain significance); an α-helix; the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain b)' region; a UniProt-annotated variant site (in arvd8; likely pathogenic; results in an unstable protein that forms perinuclear aggregates); a UniProt-annotated variant site (in arvd8 and dcwhkta; uncertain significance); a UniProt-annotated variant site (in arvd8)

Full DSP 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: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 lethal acantholytic epidermolysis bullosa arrhythmogenic right ventricular cardiomyopathy woolly hair-skin fragility syndrome

Similar variants

DSP p.Ala2294Thr Uncertain significance ★★ ⚠ same residue
DSP p.Ala2294= Likely benign ★ same residue
DSP c.1141-2A>T Likely pathogenic ★★ same condition
DSP c.1266+2T>C Likely pathogenic ★★ same condition
DSP c.1574+1G>A Likely pathogenic ★★ same condition
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2297+1G>A Likely pathogenic ★★ same condition
DSP c.2298-1G>C Likely pathogenic ★★ 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/dsp-p-ala2294gly (accessed [today's date]).

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