Is JUP p.Ser707= (c.2121C>T) pathogenic?

JUP p.Ser707= (c.2121C>T) is classified Likely benign in JUP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-17). Very rare (popmax 0.00668%, afr); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ser707= (c.2121C>T)?

JUP p.Ser707= (c.2121C>T) is associated with Cardiovascular phenotype, Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Ser707= (c.2121C>T) in the general population?

JUP p.Ser707= (c.2121C>T) is very rare (popmax 0.00668%, afr) (gnomAD).

JUP p.Ser707=

c.2121C>T · rs1477036549 · VCV1567910

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

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 · G>C here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.1	GERP -3.2
Overall
CADD	3.807	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,888 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00105% 17/1,612,392 alleles · very rare exomes 15/1,460,280 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,978
European (non-Finnish)	0.00102%	98,273

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.Ser707=
Coding: c.2121C>T
MANE Select: NM_002230
dbSNP: rs1477036549
Type: single nucleotide variant
Location: chr17:41755861 (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

Also linked: Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Ser707fs Uncertain significance ★ same residue
JUP c.1773+3G>A Uncertain significance ★★ same condition
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 c.*1026G>A Uncertain significance ★★ same condition
JUP c.*1136C>T Uncertain significance ★★ same condition
JUP c.*413C>T 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-ser707 (accessed [today's date]).

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