Is DSP p.Asp2117fs (c.6348_6351del) pathogenic?

DSP p.Asp2117fs (c.63486351del) is classified Pathogenic/Likely pathogenic in DSP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-09-29). Very rare (popmax 0.00167%, amr); Associated with DSP-related disorder.

What condition is associated with DSP p.Asp2117fs (c.6348_6351del)?

DSP p.Asp2117fs (c.6348_6351del) is associated with DSP-related disorder, cardiomyopathy (ClinVar).

How common is DSP p.Asp2117fs (c.6348_6351del) in the general population?

DSP p.Asp2117fs (c.6348_6351del) is very rare (popmax 0.00167%, amr) (gnomAD).

DSP p.Asp2117fs

c.6348_6351del · rs1759527886 · VCV978330

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 0.00167%, amr)

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	escapes	premature termination codon in the last exon (24 of 24) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.61	GERP -3.1, phastCons 0.38
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,960 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,670 alleles · very rare exomes 2/1,461,894 · genomes 1/151,776 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,960
European (non-Finnish)	0.00017%	589,971

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.Asp2117fs
Coding: c.6348_6351del
MANE Select: NM_004415
dbSNP: rs1759527886
Type: Microsatellite
Location: chr6:7583605 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2117: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); the 'binds to telomeres' region; the 'globular 2' region; the '4.5 x 38 aa tandem repeats (domain a)' 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

Similar variants

DSP p.Asp2117His Uncertain significance ★★ same residue
DSP p.Asp2117= Benign/Likely benign ★★ same residue
DSP c.2131_2132del Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1777fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Cys2497_Glu2498delinsTer Pathogenic/Likely pathogenic ★★ same condition
DSP p.Glu1213fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Glu1385fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Glu1931_Arg1932insSerTer 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-asp2117fs (accessed [today's date]).

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