Is DSP p.Arg84Ter (c.250C>T) pathogenic?

DSP p.Arg84Ter (c.250C>T) is classified Pathogenic in DSP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00133%, afr); Associated with DSP-related disorder.

How common is DSP p.Arg84Ter (c.250C>T) in the general population?

DSP p.Arg84Ter (c.250C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

DSP p.Arg84Ter

Q: What condition is associated with DSP p.Arg84Ter (c.250C>T)?

DSP p.Arg84Ter (c.250C>T) is associated with DSP-related disorder, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.250C>T · rs768521444 · VCV451211

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

DSP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 24
Splicing
SpliceAI	Δ0.74	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.10 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.5	GERP 1.7, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,066 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,140 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,066
European (non-Finnish)	0.000169%	590,009

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.Arg84Ter
Coding: c.250C>T
MANE Select: NM_004415
dbSNP: rs768521444
Type: single nucleotide variant
Location: chr6:7555797 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 84: the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; a UniProt-annotated variant site (in arvd8; uncertain significance)

Full DSP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DSP-related disorder

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

Similar variants

DSP p.Arg84Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DSP p.Arg84Gly Uncertain significance ★ same residue
DSP p.Arg84= Likely benign ★ same residue
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

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-arg84ter (accessed [today's date]).

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