Is DSP p.Arg84= (c.250C>A) pathogenic?

DSP p.Arg84= (c.250C>A) is classified Likely benign in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-29). Absent from gnomAD v4.1; Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Arg84= (c.250C>A)?

DSP p.Arg84= (c.250C>A) is associated with arrhythmogenic right ventricular dysplasia 8, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Arg84= (c.250C>A) in the general population?

DSP p.Arg84= (c.250C>A) is absent from gnomAD v4.1 (gnomAD).

DSP p.Arg84=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.250C>A · rs768521444 · VCV2117081

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

arrhythmogenic right ventricular dysplasia 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP 1.7, phastCons 1
Overall
CADD	9.925	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Arg84=
Coding: c.250C>A
MANE Select: NM_004415
dbSNP: rs768521444
Type: single nucleotide variant
Location: chr6:7555797 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 84: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance)

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

Similar variants

DSP p.Arg84Ter Pathogenic ★★ same residue
DSP p.Arg84Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Arg84Gly Uncertain significance ★ 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

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-arg84 (accessed [today's date]).

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