Is DSP p.Arg16Pro (c.47G>C) pathogenic?

DSP p.Arg16Pro (c.47G>C) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-14). AlphaMissense: likely pathogenic (0.5769); Very rare (popmax 0.00505%, amr); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Arg16Pro (c.47G>C)?

DSP p.Arg16Pro (c.47G>C) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Arg16Pro (c.47G>C) in the general population?

DSP p.Arg16Pro (c.47G>C) is very rare (popmax 0.00505%, amr) (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.Arg16Pro (c.47G>C)?

AlphaMissense predicts likely pathogenic (score 0.5769) — an in-silico prediction, not a clinical call.

DSP p.Arg16Pro

c.47G>C · rs752387234 · VCV199913

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.5769 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00505%, amr)

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Computational evidence

Protein change
AlphaMissense	0.5769	likely pathogenic
REVEL	0.46	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	24.7	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 0.00505% Admixed American · 3/59,456 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000719%

Overall 0.00131% 21/1,607,158 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00505%	19,819
Remaining individualsnot grpmax-eligible	0.00161%	62,132
European (non-Finnish)	0.00144%	69,286

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.Arg16Pro
Coding: c.47G>C
dbSNP: rs752387234
Type: single nucleotide variant
Location: chr6:7541962 (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: cardiomyopathy 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

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-arg16pro (accessed [today's date]).

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