Is JUP p.Arg142= (c.426C>A) pathogenic?

JUP p.Arg142= (c.426C>A) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). Absent from gnomAD v4.1; Associated with Naxos disease.

What condition is associated with JUP p.Arg142= (c.426C>A)?

JUP p.Arg142= (c.426C>A) is associated with Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Arg142= (c.426C>A) in the general population?

JUP p.Arg142= (c.426C>A) is absent from gnomAD v4.1 (gnomAD).

How is Naxos disease inherited?

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

JUP p.Arg142=

c.426C>A · VCV3748868

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Naxos disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -4, phastCons 0.47
Overall
CADD	6.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: JUP
Protein: p.Arg142=
Coding: c.426C>A
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41769460 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 142: the 'interaction with dsc1 and dsg1' region; a UniProt-annotated variant site (in); an α-helix

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

Disease context

Naxos disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: arrhythmogenic right ventricular dysplasia 12

For Naxos disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

JUP p.Arg142Cys Uncertain significance ★★ ⚠ same residue
JUP p.Arg142His Benign/Likely benign ★★ same residue
JUP p.Arg142Leu Uncertain significance ★ ⚠ same residue
JUP c.1773+3G>A Uncertain significance ★★ same condition
JUP c.468+4T>C Uncertain significance ★★ same condition
JUP c.707+5C>A Uncertain significance ★★ same condition
JUP c.*1026G>A Uncertain significance ★★ same condition
JUP c.*1136C>T 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/jup-p-arg142 (accessed [today's date]).

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