Is DSP p.Gln1071Ter (c.3211C>T) pathogenic?

DSP p.Gln1071Ter (c.3211C>T) is classified Pathogenic in DSP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-23). Very rare (popmax 6.84e-05%); Associated with Cardiovascular phenotype.

How common is DSP p.Gln1071Ter (c.3211C>T) in the general population?

DSP p.Gln1071Ter (c.3211C>T) is very rare (popmax 6.84e-05%) (gnomAD).

DSP p.Gln1071Ter

Q: What condition is associated with DSP p.Gln1071Ter (c.3211C>T)?

DSP p.Gln1071Ter (c.3211C>T) is associated with Cardiovascular phenotype, arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.3211C>T · rs2533922607 · VCV2926508

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 23 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	39.0	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 6.84e-05%

Overall 6.84e-05% 1/1,461,862 alleles · very rare

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.Gln1071Ter
Coding: c.3211C>T
MANE Select: NM_004415
dbSNP: rs2533922607
Type: single nucleotide variant
Location: chr6:7579401 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1071: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); the 'central fibrous rod domain' 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

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

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-gln1071ter (accessed [today's date]).

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