Is JUP p.Val486fs (c.1455_1462del) pathogenic?

JUP p.Val486fs (c.14551462del) is classified Pathogenic in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-07). Absent from gnomAD; Associated with arrhythmogenic right ventricular dysplasia 12.

What condition is associated with JUP p.Val486fs (c.1455_1462del)?

JUP p.Val486fs (c.1455_1462del) is associated with arrhythmogenic right ventricular dysplasia 12, Naxos disease (ClinVar).

How common is JUP p.Val486fs (c.1455_1462del) in the general population?

JUP p.Val486fs (c.1455_1462del) is absent from gnomAD (gnomAD).

JUP p.Val486fs

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.1455_1462del · rs1597801392 · VCV659497

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 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 8 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.4, 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: JUP
Protein: p.Val486fs
Coding: c.1455_1462del
MANE Select: NM_002230
dbSNP: rs1597801392
Type: Deletion
Location: chr17:41763018 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 486: an α-helix

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

Also linked: Naxos disease

For Inherited isolated arrhythmogenic cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: No data available

Similar variants

JUP p.Val486Gly Uncertain significance ★★ ⚠ same residue
JUP p.Val486Leu Uncertain significance ★ ⚠ same residue
JUP p.Val486Met 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

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-val486fs (accessed [today's date]).

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