Is JUP p.Pro713= (c.2139G>T) pathogenic?

JUP p.Pro713= (c.2139G>T) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 0.00669%, eas); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Pro713= (c.2139G>T)?

JUP p.Pro713= (c.2139G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JUP p.Pro713= (c.2139G>T) in the general population?

JUP p.Pro713= (c.2139G>T) is very rare (popmax 0.00669%, eas) (gnomAD).

JUP p.Pro713=

c.2139G>T · VCV3287295

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

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 -2.1	GERP -3.1
Overall
CADD	5.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,838 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000186% 3/1,613,186 alleles · very rare exomes 3/1,460,974 · genomes 0/152,212 · joint denominator

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.Pro713=
Coding: c.2139G>T
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41755843 (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

Similar variants

JUP p.Pro713Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
JUP p.Pro713Thr Uncertain significance ★ ⚠ same residue
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 p.Ala178Val Uncertain significance ★★ ⚠ same condition
JUP p.Ala263Val Uncertain significance ★★ ⚠ same condition
JUP p.Ala314Gly 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-pro713 (accessed [today's date]).

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