Is DSP p.Gln539Ter (c.1615C>T) pathogenic?

DSP p.Gln539Ter (c.1615C>T) is classified Likely pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2013-03-27). Absent from gnomAD v4.1; Associated with dilated cardiomyopathy.

What condition is associated with DSP p.Gln539Ter (c.1615C>T)?

DSP p.Gln539Ter (c.1615C>T) is associated with dilated cardiomyopathy (ClinVar).

How common is DSP p.Gln539Ter (c.1615C>T) in the general population?

DSP p.Gln539Ter (c.1615C>T) is absent from gnomAD v4.1 (gnomAD).

DSP p.Gln539Ter

c.1615C>T · rs727504498 · VCV178862

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dilated cardiomyopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 13 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.2, phastCons 1
Overall
CADD	39.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Gln539Ter
Coding: c.1615C>T
MANE Select: NM_004415
dbSNP: rs727504498
Type: single nucleotide variant
Location: chr6:7570477 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 539: an α-helix; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance); 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

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

Similar variants

DSP p.Gln539Lys Uncertain significance ★ same residue
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.939+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1045Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1934Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Cys289Ter 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-gln539ter (accessed [today's date]).

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