Is DSP p.Arg925Trp (c.2773C>T) pathogenic?

DSP p.Arg925Trp (c.2773C>T) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.2962); Rare (popmax 0.389%, afr); Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Arg925Trp (c.2773C>T)?

DSP p.Arg925Trp (c.2773C>T) is associated with arrhythmogenic right ventricular dysplasia 8, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Arg925Trp (c.2773C>T) in the general population?

DSP p.Arg925Trp (c.2773C>T) is rare (popmax 0.389%, afr) (gnomAD).

What do computational predictors say about DSP p.Arg925Trp (c.2773C>T)?

AlphaMissense predicts likely benign (score 0.2962) — an in-silico prediction, not a clinical call.

DSP p.Arg925Trp

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.2773C>T · rs145933612 · VCV44881

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.2962 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.389%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

arrhythmogenic right ventricular dysplasia 8

Computational evidence

Protein change
AlphaMissense	0.2962	likely benign
REVEL	0.147	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 -0.12	GERP -3.6, phastCons 0.15
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic
Overall
CADD	23.4	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 0.389% African / African-American · 292/75,016 alleles

Filtering AF 0.353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.338%

Overall 0.0262% 423/1,614,028 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.389%	257
Admixed American	0.065%	1,539
Remaining individualsnot grpmax-eligible	0.056%	1,786
South Asian	0.0527%	1,898
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
East Asian	0.00223%	44,862
European (non-Finnish)	0.000593%	168,569

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.Arg925Trp
Coding: c.2773C>T
MANE Select: NM_004415
dbSNP: rs145933612
Type: single nucleotide variant
Location: chr6:7576436 (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

arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma lethal acantholytic epidermolysis bullosa keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis arrhythmogenic right ventricular cardiomyopathy woolly hair-skin fragility syndrome

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSP p.Arg925Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Arg925Leu Uncertain significance ★ ⚠ same residue
DSP p.Arg925Pro Uncertain significance ★ ⚠ 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-arg925trp (accessed [today's date]).

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