Is DSP p.Arg1125del (c.3368GAA[2]) pathogenic?

DSP p.Arg1125del (c.3368GAA[2]) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-13). Very rare (popmax 8.47e-05%, nfe); Associated with Cardiovascular phenotype.

How common is DSP p.Arg1125del (c.3368GAA[2]) in the general population?

DSP p.Arg1125del (c.3368GAA[2]) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DSP p.Arg1125del

Q: What condition is associated with DSP p.Arg1125del (c.3368GAA[2])?

DSP p.Arg1125del (c.3368GAA[2]) is associated with Cardiovascular phenotype, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.3368GAA[2] · rs1405952840 · VCV1018579

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.4, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.84e-05% 1/1,461,682 alleles · very rare

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.Arg1125del
Coding: c.3368GAA[2]
MANE Select: NM_004415
dbSNP: rs1405952840
Type: Microsatellite
Location: chr6:7579557 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1125: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'central fibrous rod domain' region; the 'binds to telomeres' 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: arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

Similar variants

DSP p.Arg1125Gly Uncertain significance ★ 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
DSP p.Asp2521fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Cys2497_Glu2498delinsTer 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-arg1125del (accessed [today's date]).

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