Is JUP p.Val648= (c.1944C>G) pathogenic?

JUP p.Val648= (c.1944C>G) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). No allele count reported in gnomAD v4.1 (AN 1,614,194); Associated with Naxos disease.

What condition is associated with JUP p.Val648= (c.1944C>G)?

JUP p.Val648= (c.1944C>G) is associated with Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Val648= (c.1944C>G) in the general population?

JUP p.Val648= (c.1944C>G) is no allele count reported in gnomAD v4.1 (AN 1,614,194) (gnomAD).

How is Naxos disease inherited?

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

JUP p.Val648=

c.1944C>G · rs2544033389 · VCV2114651

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,194)

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 1.2	GERP -0.86, phastCons 1
Overall
CADD	6.622	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,194). 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.Val648=
Coding: c.1944C>G
MANE Select: NM_002230
dbSNP: rs2544033389
Type: single nucleotide variant
Location: chr17:41757517 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 648: the 'interaction with dsc1' 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.Val648Ile 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
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-val648 (accessed [today's date]).

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