JAG1 p.Pro129=
c.387G>A · rs766008628 · VCV1425290
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00333%, amr)
Conditions
1
Alagille syndrome due to a JAG1 point mutation
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 23.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00333%
Admixed American · 2/60,004 alleles
Filtering AF
0.000553%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000248%
4/1,612,436 alleles · very rare
exomes 3/1,460,216 · genomes 1/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00333% | 30,002 |
| European (non-Finnish) | 0.000169% | 589,977 |
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.Pro129=
- Coding
- c.387G>A
- MANE Select
- NM_000214
- dbSNP
- rs766008628
- Type
- single nucleotide variant
- Location
- chr20:10672701 (GRCh38)
- Gene constraint
- LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 73.02 · 7 PDB
- Residue 129
- a UniProt-annotated variant site (in algs1)
Similar variants
- JAG1 c.1395+3A>G Pathogenic ★★ same condition
- JAG1 c.2113+1G>A Likely pathogenic ★★ same condition
- JAG1 c.2113+1G>T Pathogenic/Likely pathogenic ★★ same condition
- JAG1 c.2572+1G>T Pathogenic/Likely pathogenic ★★ same condition
- JAG1 c.439+1G>A Pathogenic ★★ same condition
- JAG1 c.886+1G>A Pathogenic ★★ same condition
- JAG1 p.Arg184Cys Pathogenic/Likely pathogenic ★★ same condition
- JAG1 p.Arg184His Pathogenic/Likely pathogenic ★★ 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-pro129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown