Is DSP p.Gln471fs (c.1411_1412insT) pathogenic?

DSP p.Gln471fs (c.14111412insT) is classified Pathogenic in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-15). Absent from gnomAD; Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

How common is DSP p.Gln471fs (c.1411_1412insT) in the general population?

DSP p.Gln471fs (c.1411_1412insT) is absent from gnomAD (gnomAD).

How is Carvajal syndrome inherited?

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

DSP p.Gln471fs

Q: What condition is associated with DSP p.Gln471fs (c.1411_1412insT)?

DSP p.Gln471fs (c.1411_1412insT) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.1411_1412insT · rs1581802715 · VCV666177

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

arrhythmogenic cardiomyopathy with wooly hair and keratoderma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 11 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Gln471fs
Coding: c.1411_1412insT
MANE Select: NM_004415
dbSNP: rs1581802715
Type: Insertion
Location: chr6:7568581 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 471: a β-strand; the 'globular 1' region; the 'interaction with mapre1' region; the 'interaction with jup and pkp2' region; the sh3 domain; a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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 cardiomyopathy with wooly hair and keratoderma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arrhythmogenic right ventricular dysplasia 8

For Carvajal syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

DSP p.Gln471Arg Uncertain significance ★★ ⚠ same residue
DSP p.Gln471= Benign/Likely benign ★★ same residue
DSP p.Gln471Lys Uncertain significance ★ ⚠ same residue
DSP p.Asn2171fs Pathogenic ★★ same condition
DSP c.939+2_939+3insCC Uncertain significance ★★ same condition
DSP p.Pro450_Arg451insLeu Uncertain significance ★★ same condition
DSP c.423-16_423-15insC Benign/Likely benign ★★ same condition
DSP p.Ala1193_Lys1194insAlaGlyArgGlyGlySerArgLeuTer 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-gln471fs (accessed [today's date]).

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