Is JUP p.Ser68fs (c.201del) pathogenic?

JUP p.Ser68fs (c.201del) is classified Pathogenic in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Associated with arrhythmogenic right ventricular dysplasia 12.

What condition is associated with JUP p.Ser68fs (c.201del)?

JUP p.Ser68fs (c.201del) is associated with arrhythmogenic right ventricular dysplasia 12 (ClinVar).

JUP p.Ser68fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.201del · VCV4531653

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

arrhythmogenic right ventricular dysplasia 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.23	GERP -2.2

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

Variant & gene context

Gene: JUP
Protein: p.Ser68fs
Coding: c.201del
MANE Select: NM_002230
Type: Deletion
Location: chr17:41771654 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB

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

Disease context

arrhythmogenic right ventricular dysplasia 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

JUP p.Ser68Asn Uncertain significance ★★ ⚠ same residue
JUP p.Trp680fs Pathogenic ★★ same condition
JUP p.Asn211del Uncertain significance ★★ same condition
JUP c.1055-14del Benign/Likely benign ★★ same condition
JUP c.469-16del Likely benign ★★ same condition
JUP c.209-118_662del Likely pathogenic ★ same condition
JUP p.Ala178fs Pathogenic ★ same condition
JUP p.Ala230fs 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/jup-p-ser68fs (accessed [today's date]).

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