Is DSP p.Arg10Trp (c.28C>T) pathogenic?

DSP p.Arg10Trp (c.28C>T) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). AlphaMissense: likely pathogenic (0.8533); Very rare (popmax 8.49e-05%, nfe); Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Arg10Trp (c.28C>T)?

DSP p.Arg10Trp (c.28C>T) is associated with arrhythmogenic right ventricular dysplasia 8, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Arg10Trp (c.28C>T) in the general population?

DSP p.Arg10Trp (c.28C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about DSP p.Arg10Trp (c.28C>T)?

AlphaMissense predicts likely pathogenic (score 0.8533) — an in-silico prediction, not a clinical call.

DSP p.Arg10Trp

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.28C>T · VCV4794437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8533 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

arrhythmogenic right ventricular dysplasia 8

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.8533	likely pathogenic
REVEL	0.454	indeterminate
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	28.5	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 8.49e-05% European (non-Finnish) · 1/1,178,054 alleles

Overall 6.22e-05% 1/1,607,500 alleles · very rare exomes 1/1,457,322 · genomes 0/150,178 · 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: DSP
Protein: p.Arg10Trp
Coding: c.28C>T
MANE Select: NM_004415
Type: single nucleotide variant
Location: chr6:7541943 (GRCh38)

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: arrhythmogenic cardiomyopathy with wooly hair and keratoderma

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

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-arg10trp (accessed [today's date]).

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