Is JAG1 p.Pro552= (c.1656C>T) pathogenic?

JAG1 p.Pro552= (c.1656C>T) is classified Likely benign in JAG1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0111%, eas); Associated with Cardiovascular phenotype.

What condition is associated with JAG1 p.Pro552= (c.1656C>T)?

JAG1 p.Pro552= (c.1656C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is JAG1 p.Pro552= (c.1656C>T) in the general population?

JAG1 p.Pro552= (c.1656C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

JAG1 p.Pro552=

c.1656C>T · rs371977432 · VCV3054983

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, 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 -5.6	GERP -3.8
Overall
CADD	1.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,900 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00105% 17/1,614,002 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,980
African / African-American	0.004%	24,973
South Asian	0.0011%	91,074
European (non-Finnish)	0.000678%	147,499

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: JAG1
Protein: p.Pro552=
Coding: c.1656C>T
MANE Select: NM_000214
dbSNP: rs371977432
Type: single nucleotide variant
Location: chr20:10648024 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.02 · 7 PDB
Residue 552: the egf-like 9 domain; a disulfide bond

Full JAG1 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

Similar variants

JAG1 p.Pro552Ala Uncertain significance ★★ ⚠ same residue
JAG1 p.Pro552Leu Benign/Likely benign ★★ ⚠ same residue
JAG1 p.Pro552Ser Uncertain significance ★ ⚠ same residue
JAG1 c.886+3A>G Likely pathogenic ★★ same condition
JAG1 p.Gln457Ter Pathogenic ★★ same condition
JAG1 p.Glu353Ter Pathogenic ★★ same condition
JAG1 p.Ala1008Glu Uncertain significance ★★ same condition
JAG1 p.Ala853Thr 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/jag1-p-pro552 (accessed [today's date]).

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