Is DSP p.Ala1307Phe (c.3919_3920delinsTT) pathogenic?

DSP p.Ala1307Phe (c.39193920delinsTT) is classified Uncertain significance in DSP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). Absent from gnomAD; Associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma.

How common is DSP p.Ala1307Phe (c.3919_3920delinsTT) in the general population?

DSP p.Ala1307Phe (c.3919_3920delinsTT) 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.Ala1307Phe

Q: What condition is associated with DSP p.Ala1307Phe (c.3919_3920delinsTT)?

DSP p.Ala1307Phe (c.3919_3920delinsTT) is associated with arrhythmogenic cardiomyopathy with wooly hair and keratoderma, arrhythmogenic right ventricular dysplasia 8 (ClinVar).

c.3919_3920delinsTT · rs2533926619 · VCV2950835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -1.5, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 12 kb · p 0.0024 · regional, not allelic

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.Ala1307Phe
Coding: c.3919_3920delinsTT
MANE Select: NM_004415
dbSNP: rs2533926619
Type: Indel
Location: chr6:7580109 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1307: a UniProt-annotated variant site (in arvd8; uncertain significance); a UniProt-annotated variant site (in dcwhkta; uncertain significance); 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 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.Ala1307Ser Uncertain significance ★★ same residue
DSP p.Ala1307Thr Conflicting classifications of pathogenicity ★ same residue
DSP c.2793+1_2793+5delinsAACAAAAAG Likely pathogenic ★★ same condition
DSP c.5671_*835+957del4738insAGAACAGTCTT Pathogenic/Likely pathogenic ★★ same condition
DSP p.Tyr1139fs Pathogenic ★★ same condition
DSP c.274-8_274-7delinsAT Uncertain significance ★★ same condition
DSP p.Glu1369_Ile1370delinsAspVal Uncertain significance ★★ same condition
DSP p.Gly171Glu Uncertain significance ★★ 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-ala1307phe (accessed [today's date]).

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