Is JUP p.Ala455= (c.1365C>T) pathogenic?

JUP p.Ala455= (c.1365C>T) is classified Benign/Likely benign in JUP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). Rare (popmax 0.421%, eas); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ala455= (c.1365C>T)?

JUP p.Ala455= (c.1365C>T) is associated with Cardiovascular phenotype, Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Ala455= (c.1365C>T) in the general population?

JUP p.Ala455= (c.1365C>T) is rare (popmax 0.421%, eas) (gnomAD).

JUP p.Ala455=

c.1365C>T · rs77375949 · VCV163717

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.421%, eas)

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 -9.5	GERP -4.7
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.421% East Asian · 189/44,870 alleles

Filtering AF 0.372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.353%

Overall 0.0194% 313/1,614,174 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.421%	237
Middle Eastern	0.313%	319
Remaining individualsnot grpmax-eligible	0.0208%	4,808
African / African-American	0.016%	6,254
South Asian	0.0132%	7,590
European (non-Finnish)	0.00568%	17,612
Admixed American	0.00167%	60,030

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.Ala455=
Coding: c.1365C>T
MANE Select: NM_002230
dbSNP: rs77375949
Type: single nucleotide variant
Location: chr17:41763115 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 455: 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: Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

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
JUP c.*771G>C 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-ala455 (accessed [today's date]).

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