Is DSP p.Val1661= (c.4983C>T) pathogenic?

DSP p.Val1661= (c.4983C>T) is classified Likely benign in DSP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-05-01). Very rare (popmax 0.00771%, nfe); Associated with arrhythmogenic right ventricular dysplasia 8.

What condition is associated with DSP p.Val1661= (c.4983C>T)?

DSP p.Val1661= (c.4983C>T) is associated with arrhythmogenic right ventricular dysplasia 8, cardiomyopathy, arrhythmogenic cardiomyopathy with wooly hair and keratoderma (ClinVar).

How common is DSP p.Val1661= (c.4983C>T) in the general population?

DSP p.Val1661= (c.4983C>T) is very rare (popmax 0.00771%, nfe) (gnomAD).

DSP p.Val1661=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.4983C>T · rs755233649 · VCV519539

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00771%, nfe)

Conditions

arrhythmogenic right ventricular dysplasia 8

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -15	GERP -3.6
Overall
CADD	0.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00771% European (non-Finnish) · 91/1,180,032 alleles

Filtering AF 0.00639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00592%

Overall 0.00607% 98/1,614,122 alleles · very rare exomes 94/1,461,838 · genomes 4/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00771%	12,967
South Asian	0.00439%	22,769
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	75,038

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.Val1661=
Coding: c.4983C>T
MANE Select: NM_004415
dbSNP: rs755233649
Type: single nucleotide variant
Location: chr6:7581173 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1661: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); a UniProt-annotated variant site (in dcwhk; uncertain significance; abolishes expression in the myocardium); the 'central fibrous rod domain' region; the 'binds to telomeres' region; 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

arrhythmogenic right ventricular dysplasia 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy arrhythmogenic cardiomyopathy with wooly hair and keratoderma

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

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
DSP c.2298-1G>C Likely pathogenic ★★ same condition
DSP c.2298-2A>C Pathogenic/Likely pathogenic ★★ same condition
DSP c.2437-1G>C 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-val1661 (accessed [today's date]).

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