Is JUP p.Ser170= (c.510G>A) pathogenic?

JUP p.Ser170= (c.510G>A) is classified Benign/Likely benign in JUP (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-03). Rare (popmax 0.113%, afr); Associated with Cardiovascular phenotype.

What condition is associated with JUP p.Ser170= (c.510G>A)?

JUP p.Ser170= (c.510G>A) is associated with Cardiovascular phenotype, Naxos disease, arrhythmogenic right ventricular dysplasia 12 (ClinVar).

How common is JUP p.Ser170= (c.510G>A) in the general population?

JUP p.Ser170= (c.510G>A) is rare (popmax 0.113%, afr) (gnomAD).

JUP p.Ser170=

c.510G>A · rs140539043 · VCV239106

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.113%, afr)

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 -6.8	GERP -4.7
Overall
CADD	2.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.113% African / African-American · 85/75,062 alleles

Filtering AF 0.0938% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0866%

Overall 0.0126% 202/1,604,246 alleles · rare exomes 142/1,451,934 · genomes 60/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.113%	883
Remaining individualsnot grpmax-eligible	0.024%	4,161
South Asian	0.0209%	4,793
East Asian	0.0201%	4,987
Finnishnot grpmax-eligible	0.0129%	7,771
European (non-Finnish)	0.00559%	17,878
Admixed American	0.00167%	60,008

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.Ser170=
Coding: c.510G>A
MANE Select: NM_002230
dbSNP: rs140539043
Type: single nucleotide variant
Location: chr17:41769166 (GRCh38)
Gene constraint: LOEUF 0.533 · pLI 0.74 (gnomAD)
Structure: AlphaFold pLDDT 80.88 · 1 PDB
Residue 170: 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

Also linked: Naxos disease arrhythmogenic right ventricular dysplasia 12

Similar variants

JUP p.Ser170Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
JUP p.Ser170Trp 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-ser170 (accessed [today's date]).

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