Is JUP p.Ala347= (c.1041C>T) pathogenic?

JUP p.Ala347= (c.1041C>T) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-13). Very rare (popmax 0.000254%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ala347= (c.1041C>T)?

JUP p.Ala347= (c.1041C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JUP p.Ala347= (c.1041C>T) in the general population?

JUP p.Ala347= (c.1041C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

JUP p.Ala347=

c.1041C>T · VCV3862356

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 5.8	GERP 0.1, phastCons 1
Overall
CADD	12.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,024 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,874 alleles · very rare

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.Ala347=
Coding: c.1041C>T
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41764936 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 347: 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.Ala347Val Uncertain significance ★★ same residue
JUP p.Ala347Thr 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

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-ala347 (accessed [today's date]).

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