Is DSP p.Val712fs (c.2135_2136del) pathogenic?

DSP p.Val712fs (c.21352136del) is classified Pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-29). Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Val712fs (c.2135_2136del)?

DSP p.Val712fs (c.2135_2136del) is associated with arrhythmogenic right ventricular dysplasia 8, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

DSP p.Val712fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.2135_2136del · VCV4787894

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

arrhythmogenic right ventricular dysplasia 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 16 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 0.27, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DSP
Protein: p.Val712fs
Coding: c.2135_2136del
MANE Select: NM_004415
Type: Microsatellite
Location: chr6:7574087 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 712: a UniProt-annotated variant site (in arvd8; uncertain significance); the 'globular 1' region; the 'interaction with mapre1' region; a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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: arrhythmogenic cardiomyopathy with wooly hair and keratoderma

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

DSP p.Val712Leu Uncertain significance ★★ ⚠ same residue
DSP p.Val712Ala Uncertain significance ★ ⚠ same residue
DSP p.Val712Met Conflicting classifications of pathogenicity ★ same residue
DSP c.2131_2132del Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1777fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg2394fs Pathogenic ★★ same condition
DSP p.Asn1526_Lys1527insTer Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asn956_Ser957insTer 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-val712fs (accessed [today's date]).

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