Is DSP p.Phe2544fs (c.7629del) pathogenic?

DSP p.Phe2544fs (c.7629del) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-23). Very rare (popmax 6.2e-05%); Associated with cardiomyopathy.

What condition is associated with DSP p.Phe2544fs (c.7629del)?

DSP p.Phe2544fs (c.7629del) is associated with cardiomyopathy (ClinVar).

How common is DSP p.Phe2544fs (c.7629del) in the general population?

DSP p.Phe2544fs (c.7629del) is very rare (popmax 6.2e-05%) (gnomAD).

DSP p.Phe2544fs

c.7629del · VCV4756376

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

cardiomyopathy

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 7.9	GERP -0.54, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,156 alleles · very rare exomes 1/1,461,894 · genomes 0/152,262 · joint denominator

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.Phe2544fs
Coding: c.7629del
MANE Select: NM_004415
Type: Deletion
Location: chr6:7584891 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2544: 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); a UniProt-annotated variant site (in ebla; uncertain significance); the 'binds to telomeres' region; the 'globular 2' 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

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DSP p.Phe2544Leu Uncertain significance ★★ ⚠ same residue
DSP c.2131-3_2131del Likely pathogenic ★★ same condition
DSP p.Asn1346fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Gln1311fs Pathogenic ★★ same condition
DSP p.Glu1337fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Gly1600fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Gly2133fs Pathogenic/Likely pathogenic ★★ same condition
DSP p.Ile156fs 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-phe2544fs (accessed [today's date]).

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