Is DSP p.Tyr891= (c.2673T>C) pathogenic?

DSP p.Tyr891= (c.2673T>C) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.35%, afr); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Tyr891= (c.2673T>C)?

DSP p.Tyr891= (c.2673T>C) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Tyr891= (c.2673T>C) in the general population?

DSP p.Tyr891= (c.2673T>C) is low-frequency (popmax 2.35%, afr) (gnomAD).

How is Carvajal syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DSP p.Tyr891=

c.2673T>C · rs146407262 · VCV44878

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.35%, afr)

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

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 -3.9	GERP -3.6
Overall
CADD	0.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.35% African / African-American · 1,762/75,064 alleles

Filtering AF 2.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.22%

Overall 0.119% 1,914/1,614,156 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.35%	43
Remaining individualsnot grpmax-eligible	0.123%	812
Admixed American	0.0983%	1,017
Middle Eastern	0.033%	3,030
European (non-Finnish)	0.0011%	90,770
South Asian	0.0011%	91,084

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.Tyr891=
Coding: c.2673T>C
MANE Select: NM_004415
dbSNP: rs146407262
Type: single nucleotide variant
Location: chr6:7576336 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 891: 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

arrhythmogenic cardiomyopathy with wooly hair and keratoderma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic right ventricular dysplasia 8

For Carvajal syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

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
DSP c.2437-1G>C 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-tyr891 (accessed [today's date]).

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