Is DSP p.Cys482Gly (c.1444T>G) pathogenic?

DSP p.Cys482Gly (c.1444T>G) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-17). AlphaMissense: ambiguous (0.5288); Very rare (popmax 0.000496%); Associated with cardiomyopathy.

What condition is associated with DSP p.Cys482Gly (c.1444T>G)?

DSP p.Cys482Gly (c.1444T>G) is associated with cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Cys482Gly (c.1444T>G) in the general population?

DSP p.Cys482Gly (c.1444T>G) is very rare (popmax 0.000496%) (gnomAD).

What do computational predictors say about DSP p.Cys482Gly (c.1444T>G)?

AlphaMissense predicts ambiguous (score 0.5288) — an in-silico prediction, not a clinical call.

DSP p.Cys482Gly

c.1444T>G · rs746816016 · VCV3073128

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000496%)

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.5288	ambiguous
REVEL	0.575	indeterminate
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	24.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000496%

Overall 0.000496% 8/1,613,890 alleles · very rare

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.Cys482Gly
Coding: c.1444T>G
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

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

Also linked: arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Similar variants

DSP p.Cys482Arg 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-cys482gly (accessed [today's date]).

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