Is DSP p.Gln2452Pro (c.7355A>C) pathogenic?

DSP p.Gln2452Pro (c.7355A>C) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely benign (0.0726); Very rare (popmax 8.47e-05%, nfe); Associated with cardiomyopathy.

What condition is associated with DSP p.Gln2452Pro (c.7355A>C)?

DSP p.Gln2452Pro (c.7355A>C) is associated with cardiomyopathy (ClinVar).

How common is DSP p.Gln2452Pro (c.7355A>C) in the general population?

DSP p.Gln2452Pro (c.7355A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DSP p.Gln2452Pro (c.7355A>C)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

DSP p.Gln2452Pro

c.7355A>C · rs1759567864 · VCV919381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.151	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 1.8, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 1,308 bp · p 0.26 · regional, not allelic
Overall
CADD	18.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,002 alleles

Overall 6.84e-05% 1/1,461,788 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.Gln2452Pro
Coding: c.7355A>C
MANE Select: NM_004415
dbSNP: rs1759567864
Type: single nucleotide variant
Location: chr6:7584617 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2452: 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.Gln2452His Uncertain significance ★ ⚠ same residue
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2437-1G>C Likely pathogenic ★★ same condition
DSP c.273+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.939+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1113Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1267Ter Pathogenic/Likely pathogenic ★★ same condition
DSP p.Arg1269Ter 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-gln2452pro (accessed [today's date]).

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