Is DSP p.Cys482Arg (c.1444T>C) pathogenic?

DSP p.Cys482Arg (c.1444T>C) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-25). AlphaMissense: likely pathogenic (0.9972); Absent from gnomAD v4.1; Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Cys482Arg (c.1444T>C)?

DSP p.Cys482Arg (c.1444T>C) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Cys482Arg (c.1444T>C) in the general population?

DSP p.Cys482Arg (c.1444T>C) is absent from gnomAD v4.1 (gnomAD).

How is Carvajal syndrome inherited?

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

What do computational predictors say about DSP p.Cys482Arg (c.1444T>C)?

AlphaMissense predicts likely pathogenic (score 0.9972) — an in-silico prediction, not a clinical call.

DSP p.Cys482Arg

c.1444T>C · rs746816016 · VCV626738

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9972 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Computational evidence

Protein change
AlphaMissense	0.9972	likely pathogenic · top 2% in DSP
REVEL	0.816	moderately pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DSP
Protein: p.Cys482Arg
Coding: c.1444T>C
MANE Select: NM_004415
dbSNP: rs746816016
Type: single nucleotide variant
Location: chr6:7569210 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 482: a β-strand; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the sh3 domain; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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 p.Cys482Gly Uncertain significance ★★ same residue
DSP p.Cys482Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Cys482fs Pathogenic ★ 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-cys482arg (accessed [today's date]).

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