Is JUP p.Arg86= (c.258G>A) pathogenic?

JUP p.Arg86= (c.258G>A) is classified Likely benign in JUP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0481%, afr); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Arg86= (c.258G>A)?

JUP p.Arg86= (c.258G>A) is associated with Cardiovascular phenotype, Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Arg86= (c.258G>A) in the general population?

JUP p.Arg86= (c.258G>A) is ultra-rare (popmax 0.0481%, afr) (gnomAD).

JUP p.Arg86=

c.258G>A · rs147159111 · VCV391993

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0481%, afr)

Conditions

Cardiovascular phenotype

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 0.24	GERP -3.7, phastCons 0.98
Overall
CADD	9.626	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0481% African / African-American · 36/74,922 alleles

Filtering AF 0.0357% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00274% 44/1,606,218 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0481%	2,081
Admixed American	0.00685%	14,591
Remaining individualsnot grpmax-eligible	0.00643%	15,551

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.Arg86=
Coding: c.258G>A
MANE Select: NM_002230
dbSNP: rs147159111
Type: single nucleotide variant
Location: chr17:41769628 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB

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

Disease context

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

Also linked: Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Arg86Trp Uncertain significance ★★ same residue
JUP p.Arg86Gln 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.-1G>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-arg86 (accessed [today's date]).

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