Is JUP p.Val232Asp (c.695T>A) pathogenic?

JUP p.Val232Asp (c.695T>A) is classified Uncertain significance in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.9998); Very rare (popmax 8.5e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Val232Asp (c.695T>A)?

JUP p.Val232Asp (c.695T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is JUP p.Val232Asp (c.695T>A) in the general population?

JUP p.Val232Asp (c.695T>A) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

What do computational predictors say about JUP p.Val232Asp (c.695T>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

JUP p.Val232Asp

c.695T>A · VCV3895185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 5% in JUP
REVEL	0.911	moderately pathogenic-leaning
SaProt	LLR -14.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 16 kb · p 5.2e-07 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,892 alleles

Overall 6.23e-05% 1/1,606,208 alleles · very rare exomes 1/1,453,964 · genomes 0/152,244 · 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.Val232Asp
Coding: c.695T>A
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41768981 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 232: the 'interaction with dsc1 and dsg1' 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

Similar variants

JUP p.Val232Ile Conflicting classifications of pathogenicity ★ ⚠ 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
JUP p.Ala347Val 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-val232asp (accessed [today's date]).

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