Is DSP p.Cys174= (c.522T>C) pathogenic?

DSP p.Cys174= (c.522T>C) is classified Benign/Likely benign in DSP (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-02). Rare (popmax 0.43%, afr); Associated with Cardiovascular phenotype.

What condition is associated with DSP p.Cys174= (c.522T>C)?

DSP p.Cys174= (c.522T>C) is associated with Cardiovascular phenotype, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Cys174= (c.522T>C) in the general population?

DSP p.Cys174= (c.522T>C) is rare (popmax 0.43%, afr) (gnomAD).

DSP p.Cys174=

c.522T>C · rs144781697 · VCV163239

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.43%, afr)

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 0.41	GERP -4.3, phastCons 1
Overall
CADD	7.358	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.43% African / African-American · 323/75,050 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.377%

Overall 0.021% 339/1,613,826 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.43%	232
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Admixed American	0.005%	20,008
South Asian	0.0011%	91,064

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.Cys174=
Coding: c.522T>C
MANE Select: NM_004415
dbSNP: rs144781697
Type: single nucleotide variant
Location: chr6:7559325 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 174: 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)

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 keratosis palmoplantaris striata 2 cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis woolly hair-skin fragility syndrome

Similar variants

DSP p.Cys174Ser Uncertain significance ★★ ⚠ same residue
DSP p.Cys174Ter Pathogenic ★ same residue
DSP p.Cys174Phe Conflicting classifications of pathogenicity ★ ⚠ 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-cys174 (accessed [today's date]).

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