Is JUP p.Pro238Ala (c.712C>G) pathogenic?

JUP p.Pro238Ala (c.712C>G) is classified Uncertain significance in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: ambiguous (0.3572); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Pro238Ala (c.712C>G)?

JUP p.Pro238Ala (c.712C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is JUP p.Pro238Ala (c.712C>G) in the general population?

JUP p.Pro238Ala (c.712C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about JUP p.Pro238Ala (c.712C>G)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

JUP p.Pro238Ala

c.712C>G · VCV4089550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.428	indeterminate
SaProt	LLR -8.55	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 16 kb · p 5.2e-07 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: JUP
Protein: p.Pro238Ala
Coding: c.712C>G
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41767576 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 238: the 'interaction with dsc1 and dsg1' region

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 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
JUP p.Ala347Val Uncertain significance ★★ same condition
JUP p.Ala516Asp 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-pro238ala (accessed [today's date]).

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