Is JUP p.Asp135= (c.405C>T) pathogenic?

JUP p.Asp135= (c.405C>T) is classified Benign/Likely benign in JUP (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-03-27). Common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Asp135= (c.405C>T)?

JUP p.Asp135= (c.405C>T) is associated with Cardiovascular phenotype, cardiomyopathy, Naxos disease (ClinVar).

JUP p.Asp135=

Q: How common is JUP p.Asp135= (c.405C>T) in the general population?

JUP p.Asp135= (c.405C>T) is common (popmax 10.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.405C>T · rs17850807 · VCV45850

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 10.6%, 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 -4.7	GERP -4.7
Overall
CADD	0.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.6% African / African-American · 7,976/75,004 alleles

Filtering AF 10.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.4%

Overall 0.577% 9,311/1,613,032 alleles · common exomes 4,594/1,460,742 · genomes 4,717/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.6%	9
Admixed American	0.936%	107
Remaining individualsnot grpmax-eligible	0.753%	133
Middle Eastern	0.264%	379
European (non-Finnish)	0.0232%	4,306
South Asian	0.0143%	6,989
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,568

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.Asp135=
Coding: c.405C>T
MANE Select: NM_002230
dbSNP: rs17850807
Type: single nucleotide variant
Location: chr17:41769481 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 135: 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

Also linked: cardiomyopathy Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Asp135His 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-asp135 (accessed [today's date]).

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