Is JUP p.Pro156= (c.468G>A) pathogenic?

JUP p.Pro156= (c.468G>A) is classified Conflicting classifications of pathogenicity in JUP (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-05-19). Ultra-rare (popmax 0.0165%, mid); Associated with arrhythmogenic right ventricular dysplasia 12.

What condition is associated with JUP p.Pro156= (c.468G>A)?

JUP p.Pro156= (c.468G>A) is associated with arrhythmogenic right ventricular dysplasia 12, Naxos disease (ClinVar).

How common is JUP p.Pro156= (c.468G>A) in the general population?

JUP p.Pro156= (c.468G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

JUP p.Pro156=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.468G>A · rs886037753 · VCV212749

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

arrhythmogenic right ventricular dysplasia 12

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.87	donor gain · deltas
Pangolin	Δ0.75	loss · gain 0.74 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 2.3, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000621% 10/1,610,584 alleles · ultra-rare exomes 10/1,458,306 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
European (non-Finnish)	0.000763%	130,983

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.Pro156=
Coding: c.468G>A
MANE Select: NM_002230
dbSNP: rs886037753
Type: single nucleotide variant
Location: chr17:41769418 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 156: 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

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.Pro156Leu Uncertain significance ★★ ⚠ same residue
JUP p.Pro156fs Conflicting classifications of pathogenicity ★ 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

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-pro156 (accessed [today's date]).

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