Is JUP p.Asp71= (c.213T>C) pathogenic?

JUP p.Asp71= (c.213T>C) is classified Benign in JUP (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Common (popmax 88.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Asp71= (c.213T>C)?

JUP p.Asp71= (c.213T>C) is associated with Cardiovascular phenotype, cardiomyopathy, Naxos disease (ClinVar).

JUP p.Asp71=

Q: How common is JUP p.Asp71= (c.213T>C) in the general population?

JUP p.Asp71= (c.213T>C) is common (popmax 88.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.213T>C · rs7405731 · VCV45845

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 88.6%, afr) — too common for a highly-penetrant pathogenic allele

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 2.4	GERP -2.3, phastCons 1
Overall
CADD	9.513	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 88.6% African / African-American · 66,420/75,000 alleles

Filtering AF 88% ClinGen BA1/BS1 input FAF95, joint · FAF99 87.8%

Overall 75.2% 1,208,750/1,606,858 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	88.6%	1
Ashkenazi Jewishnot grpmax-eligible	81.5%	1
Middle Eastern	80.6%	1
European (non-Finnish)	76.3%	1
South Asian	75.8%	1
Remaining individualsnot grpmax-eligible	75.8%	1
Amishnot grpmax-eligible	75.2%	1
Finnishnot grpmax-eligible	68.2%	1
Admixed American	56.9%	2
East Asian	51.8%	2

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.Asp71=
Coding: c.213T>C
MANE Select: NM_002230
dbSNP: rs7405731
Type: single nucleotide variant
Location: chr17:41769673 (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: cardiomyopathy Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Asp71Tyr Uncertain significance ★★ ⚠ same residue
JUP p.Asp71Glu 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

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-asp71 (accessed [today's date]).

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