Is DSP p.Arg16Ser (c.46C>A) pathogenic?

DSP p.Arg16Ser (c.46C>A) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.733); Ultra-rare (popmax 0.0144%, sas); Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

What condition is associated with DSP p.Arg16Ser (c.46C>A)?

DSP p.Arg16Ser (c.46C>A) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, cardiomyopathy, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

How common is DSP p.Arg16Ser (c.46C>A) in the general population?

DSP p.Arg16Ser (c.46C>A) is ultra-rare (popmax 0.0144%, sas) (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.Arg16Ser (c.46C>A)?

AlphaMissense predicts likely pathogenic (score 0.733) — an in-silico prediction, not a clinical call.

DSP p.Arg16Ser

c.46C>A · rs754773488 · VCV629716

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.733 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.733	likely pathogenic
REVEL	0.357	indeterminate
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 29 kb · p 0.14 · regional, not allelic
Overall
CADD	26.2	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 0.0144% South Asian · 13/90,124 alleles

Filtering AF 0.00853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00668%

Overall 0.000808% 13/1,608,152 alleles · ultra-rare exomes 13/1,455,812 · genomes 0/152,340 · joint denominator

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.Arg16Ser
Coding: c.46C>A
MANE Select: NM_004415
dbSNP: rs754773488
Type: single nucleotide variant
Location: chr6:7541961 (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

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-arg16ser (accessed [today's date]).

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