Is JUP p.Asp268= (c.804C>T) pathogenic?

JUP p.Asp268= (c.804C>T) is classified Likely benign in JUP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-12). Very rare (popmax 0.00549%, sas); Associated with arrhythmogenic right ventricular dysplasia 12.

What condition is associated with JUP p.Asp268= (c.804C>T)?

JUP p.Asp268= (c.804C>T) is associated with arrhythmogenic right ventricular dysplasia 12, Naxos disease (ClinVar).

How common is JUP p.Asp268= (c.804C>T) in the general population?

JUP p.Asp268= (c.804C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

JUP p.Asp268=

Q: How is Inherited isolated arrhythmogenic cardiomyopathy inherited?

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

c.804C>T · rs782667629 · VCV221029

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

arrhythmogenic right ventricular dysplasia 12

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 -9.6	GERP -4.7
Overall
CADD	1.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,090 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00316% 51/1,613,886 alleles · very rare exomes 48/1,461,830 · genomes 3/152,056 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,218
African / African-American	0.00534%	18,718
European (non-Finnish)	0.00339%	29,500
Remaining individualsnot grpmax-eligible	0.0032%	31,242

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.Asp268=
Coding: c.804C>T
MANE Select: NM_002230
dbSNP: rs782667629
Type: single nucleotide variant
Location: chr17:41767484 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 268: the 'interaction with dsc1 and dsg1' region

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.Asp268Asn 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-asp268 (accessed [today's date]).

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