Is JAG1 p.Asp487= (c.1461C>T) pathogenic?

JAG1 p.Asp487= (c.1461C>T) is classified Likely benign in JAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-30). Very rare (popmax 8.47e-05%, nfe); Associated with Alagille syndrome due to a JAG1 point mutation.

What condition is associated with JAG1 p.Asp487= (c.1461C>T)?

JAG1 p.Asp487= (c.1461C>T) is associated with Alagille syndrome due to a JAG1 point mutation (ClinVar).

How common is JAG1 p.Asp487= (c.1461C>T) in the general population?

JAG1 p.Asp487= (c.1461C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

JAG1 p.Asp487=

c.1461C>T · rs2514517239 · VCV2144006

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Overall
CADD	12.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,966 alleles

Overall 6.2e-05% 1/1,614,114 alleles · very rare exomes 1/1,461,812 · genomes 0/152,302 · joint denominator

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.Asp487=
Coding: c.1461C>T
MANE Select: NM_000214
dbSNP: rs2514517239
Type: single nucleotide variant
Location: chr20:10648657 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.02 · 7 PDB
Residue 487: the egf-like 8; calcium-binding domain

Full JAG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Alagille syndrome due to a JAG1 point mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp487 (accessed [today's date]).

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