Is JUP p.Ala617= (c.1851G>A) pathogenic?

JUP p.Ala617= (c.1851G>A) is classified Likely benign in JUP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-05). Very rare (popmax 0.0022%, sas); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ala617= (c.1851G>A)?

JUP p.Ala617= (c.1851G>A) is associated with Cardiovascular phenotype, Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Ala617= (c.1851G>A) in the general population?

JUP p.Ala617= (c.1851G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

JUP p.Ala617=

c.1851G>A · rs1031612674 · VCV381996

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 -15	GERP -4.4
Overall
CADD	0.517	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,028 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00167% 27/1,613,194 alleles · very rare exomes 25/1,461,014 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,514
European (non-Finnish)	0.00203%	49,148
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Ala617=
Coding: c.1851G>A
MANE Select: NM_002230
dbSNP: rs1031612674
Type: single nucleotide variant
Location: chr17:41757707 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 617: the 'interaction with dsc1' region; an α-helix

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.Ala617Thr Uncertain significance ★★ ⚠ same residue
JUP p.Ala617Val 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-ala617 (accessed [today's date]).

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