Is JAG1 p.Arg705= (c.2115T>C) pathogenic?

JAG1 p.Arg705= (c.2115T>C) is classified Likely benign in JAG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Absent from gnomAD v4.1; Associated with Alagille syndrome due to a JAG1 point mutation.

What condition is associated with JAG1 p.Arg705= (c.2115T>C)?

JAG1 p.Arg705= (c.2115T>C) is associated with Alagille syndrome due to a JAG1 point mutation (ClinVar).

How common is JAG1 p.Arg705= (c.2115T>C) in the general population?

JAG1 p.Arg705= (c.2115T>C) is absent from gnomAD v4.1 (gnomAD).

JAG1 p.Arg705=

c.2115T>C · rs2122603103 · VCV1153848

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	<0.2	all four deltas below 0.2 · A>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP 0.58, phastCons 1
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: JAG1
Protein: p.Arg705=
Coding: c.2115T>C
MANE Select: NM_000214
dbSNP: rs2122603103
Type: single nucleotide variant
Location: chr20:10645255 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.02 · 7 PDB
Residue 705: the egf-like 13 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 p.Arg705His Uncertain significance ★★ ⚠ same residue
JAG1 p.Arg705fs Pathogenic ★ same residue
JAG1 p.Arg705Cys Uncertain significance ★ ⚠ same residue
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

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-arg705 (accessed [today's date]).

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