Is DSP p.Arg925Gln (c.2774G>A) pathogenic?

DSP p.Arg925Gln (c.2774G>A) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 14 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1291); Rare (popmax 0.528%, mid); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Arg925Gln (c.2774G>A)?

DSP p.Arg925Gln (c.2774G>A) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Arg925Gln (c.2774G>A) in the general population?

DSP p.Arg925Gln (c.2774G>A) is rare (popmax 0.528%, mid) (gnomAD).

What do computational predictors say about DSP p.Arg925Gln (c.2774G>A)?

AlphaMissense predicts likely benign (score 0.1291) — an in-silico prediction, not a clinical call.

DSP p.Arg925Gln

c.2774G>A · rs139799237 · VCV199875

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.1291 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.528%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1291	likely benign
REVEL	0.058	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.8	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 0.528% Middle Eastern · 32/6,060 alleles

Filtering AF 0.384% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0234% 377/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.528%	189
South Asian	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0352%	2,841
European (non-Finnish)	0.0209%	4,777
Admixed American	0.02%	5,001
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
African / African-American	0.00533%	18,753
East Asian	0.00223%	44,864

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.Arg925Gln
Coding: c.2774G>A
MANE Select: NM_004415
dbSNP: rs139799237
Type: single nucleotide variant
Location: chr6:7576437 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 925: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'globular 1' 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 familial restrictive cardiomyopathy woolly hair-skin fragility syndrome

Similar variants

DSP p.Arg925Leu Uncertain significance ★ ⚠ same residue
DSP p.Arg925Pro Uncertain significance ★ ⚠ same residue
DSP p.Arg925Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Arg925= 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

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-arg925gln (accessed [today's date]).

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