Is JUP p.Val242= (c.726C>T) pathogenic?

JUP p.Val242= (c.726C>T) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-22). Very rare (popmax 0.000231%, nfe); Associated with Naxos disease.

What condition is associated with JUP p.Val242= (c.726C>T)?

JUP p.Val242= (c.726C>T) is associated with Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Val242= (c.726C>T) in the general population?

JUP p.Val242= (c.726C>T) is very rare (popmax 0.000231%, nfe) (gnomAD).

How is Naxos disease inherited?

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

JUP p.Val242=

c.726C>T · rs2143652970 · VCV1081261

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000231%, nfe)

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 0.63	GERP -1.1, phastCons 1
Overall
CADD	10.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000231% European (non-Finnish) · 2/865,508 alleles

Filtering AF 3.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.00028% 3/1,072,792 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00215%	46,438
European (non-Finnish)grpmax	0.000231%	432,754

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: JUP
Protein: p.Val242=
Coding: c.726C>T
MANE Select: NM_002230
dbSNP: rs2143652970
Type: single nucleotide variant
Location: chr17:41767562 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 242: the 'interaction with dsc1 and dsg1' region; 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.Val242Phe 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
JUP c.*413C>T Uncertain significance ★★ same condition
JUP c.*771G>C 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-val242 (accessed [today's date]).

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