Is DSP p.Glu1213fs (c.3639_3640del) pathogenic?

DSP p.Glu1213fs (c.36393640del) is classified Pathogenic/Likely pathogenic in DSP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-11). Very rare (popmax 6.84e-05%); Associated with DSP-related disorder.

What condition is associated with DSP p.Glu1213fs (c.3639_3640del)?

DSP p.Glu1213fs (c.3639_3640del) is associated with DSP-related disorder, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Glu1213fs (c.3639_3640del) in the general population?

DSP p.Glu1213fs (c.3639_3640del) is very rare (popmax 6.84e-05%) (gnomAD).

DSP p.Glu1213fs

c.3639_3640del · rs2113692271 · VCV1445018

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

DSP-related disorder

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 23 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP 0.74, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,870 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.Glu1213fs
Coding: c.3639_3640del
MANE Select: NM_004415
dbSNP: rs2113692271
Type: Microsatellite
Location: chr6:7579826 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1213: 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

DSP-related disorder

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

Similar variants

DSP p.Glu1213= Likely benign ★ 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.Asp2117fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Asp2521fs 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-glu1213fs (accessed [today's date]).

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