Is JUP p.Ser225= (c.675G>T) pathogenic?

JUP p.Ser225= (c.675G>T) is classified Likely benign in JUP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ser225= (c.675G>T)?

JUP p.Ser225= (c.675G>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JUP p.Ser225= (c.675G>T) in the general population?

JUP p.Ser225= (c.675G>T) is absent from gnomAD v4.1 (gnomAD).

JUP p.Ser225=

c.675G>T · VCV4089568

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -7.2	GERP -4.7
Overall
CADD	0.861	PHRED · no single calibrated threshold — expert panels disagree

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.Ser225=
Coding: c.675G>T
MANE Select: NM_002230
Type: single nucleotide variant
Location: chr17:41769001 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 225: 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 p.Ser225Leu 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
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-ser225 (accessed [today's date]).

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