Is DSP p.Arg16Cys (c.46C>T) pathogenic?

DSP p.Arg16Cys (c.46C>T) is classified Conflicting classifications of pathogenicity in DSP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-12-20). AlphaMissense: ambiguous (0.4207); No allele count reported in gnomAD v4.1 (AN 1,608,152); Associated with Cardiovascular phenotype.

How common is DSP p.Arg16Cys (c.46C>T) in the general population?

DSP p.Arg16Cys (c.46C>T) is no allele count reported in gnomAD v4.1 (AN 1,608,152) (gnomAD).

What do computational predictors say about DSP p.Arg16Cys (c.46C>T)?

AlphaMissense predicts ambiguous (score 0.4207) — an in-silico prediction, not a clinical call.

DSP p.Arg16Cys

Q: What condition is associated with DSP p.Arg16Cys (c.46C>T)?

DSP p.Arg16Cys (c.46C>T) is associated with Cardiovascular phenotype, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.46C>T · rs754773488 · VCV1742538

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4207 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,608,152)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.4207	ambiguous
REVEL	0.468	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	29.4	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

No allele count reported in gnomAD v4.1 (AN 1,608,152). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DSP
Protein: p.Arg16Cys
Coding: c.46C>T
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

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

Also linked: arrhythmogenic cardiomyopathy with wooly hair and keratoderma arrhythmogenic right ventricular dysplasia 8

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-arg16cys (accessed [today's date]).

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