Is DSP p.Asp1772= (c.5316T>C) pathogenic?

DSP p.Asp1772= (c.5316T>C) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2025-12-23). Ultra-rare (popmax 0.0276%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Asp1772= (c.5316T>C)?

DSP p.Asp1772= (c.5316T>C) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Asp1772= (c.5316T>C) in the general population?

DSP p.Asp1772= (c.5316T>C) is ultra-rare (popmax 0.0276%, nfe) (gnomAD).

DSP p.Asp1772=

c.5316T>C · rs376186141 · VCV357958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0276%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP -0.97, phastCons 1
Overall
CADD	11.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0276% European (non-Finnish) · 326/1,180,016 alleles

Filtering AF 0.0251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0241%

Overall 0.0214% 346/1,613,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0276%	3,620
Remaining individualsnot grpmax-eligible	0.016%	6,248
Finnishnot grpmax-eligible	0.0156%	6,401

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.Asp1772=
Coding: c.5316T>C
MANE Select: NM_004415
dbSNP: rs376186141
Type: single nucleotide variant
Location: chr6:7581506 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1772: 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 '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

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

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8 lethal acantholytic epidermolysis bullosa woolly hair-skin fragility syndrome

Similar variants

DSP p.Asp1772Gly Uncertain significance ★ ⚠ same residue
DSP c.1141-2A>T Likely pathogenic ★★ same condition
DSP c.1266+2T>C Likely pathogenic ★★ same condition
DSP c.1574+1G>A Likely pathogenic ★★ same condition
DSP c.2130+1G>A Pathogenic/Likely pathogenic ★★ same condition
DSP c.2297+1G>A Likely pathogenic ★★ same condition
DSP c.2298-1G>C Likely pathogenic ★★ same condition
DSP c.2298-2A>C 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-asp1772 (accessed [today's date]).

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