Is DSP p.Cys954= (c.2862C>T) pathogenic?

DSP p.Cys954= (c.2862C>T) is classified Benign in DSP (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-04). Common (popmax 37.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Cys954= (c.2862C>T)?

DSP p.Cys954= (c.2862C>T) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

DSP p.Cys954=

Q: How common is DSP p.Cys954= (c.2862C>T) in the general population?

DSP p.Cys954= (c.2862C>T) is common (popmax 37.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2862C>T · rs2064217 · VCV44886

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Common

common (popmax 37.4%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.29	GERP -0.76, phastCons 0.42
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37.4% African / African-American · 27,966/74,756 alleles

Filtering AF 37% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.9%

Overall 23.9% 383,963/1,608,878 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	37.4%	3
South Asian	26.4%	4
Finnishnot grpmax-eligible	24.7%	4
Remaining individualsnot grpmax-eligible	24.2%	4
Amishnot grpmax-eligible	23.8%	4
Admixed American	23.5%	4
Middle Eastern	23.5%	4
European (non-Finnish)	23%	4
Ashkenazi Jewishnot grpmax-eligible	22.9%	4
East Asian	18.9%	5

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.Cys954=
Coding: c.2862C>T
MANE Select: NM_004415
dbSNP: rs2064217
Type: single nucleotide variant
Location: chr6:7577027 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 954: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'globular 1' 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.Cys954Phe Uncertain significance ★ same residue
DSP p.Cys954Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Cys954Arg Likely benign ★ 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

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-cys954 (accessed [today's date]).

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