Is DSP p.Asp25Tyr (c.73G>T) pathogenic?

DSP p.Asp25Tyr (c.73G>T) is classified Uncertain significance in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.5716); Absent from gnomAD v4.1; Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

How common is DSP p.Asp25Tyr (c.73G>T) in the general population?

DSP p.Asp25Tyr (c.73G>T) 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.Asp25Tyr (c.73G>T)?

AlphaMissense predicts likely pathogenic (score 0.5716) — an in-silico prediction, not a clinical call.

DSP p.Asp25Tyr

Q: What condition is associated with DSP p.Asp25Tyr (c.73G>T)?

DSP p.Asp25Tyr (c.73G>T) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.73G>T · rs2113628779 · VCV1463598

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5716 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Computational evidence

Protein change
AlphaMissense	0.5716	likely pathogenic
REVEL	0.442	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	25.2	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

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.Asp25Tyr
Coding: c.73G>T
dbSNP: rs2113628779
Type: single nucleotide variant
Location: chr6:7541988 (GRCh38)

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: arrhythmogenic right ventricular dysplasia 8

For Carvajal syndrome (Orphanet):

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

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-asp25tyr (accessed [today's date]).

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