Is JAG1 p.Ser32= (c.96G>C) pathogenic?

JAG1 p.Ser32= (c.96G>C) is classified Conflicting classifications of pathogenicity in JAG1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-05). Very rare (popmax 0.0011%, sas); Associated with Alagille syndrome due to a JAG1 point mutation.

What condition is associated with JAG1 p.Ser32= (c.96G>C)?

JAG1 p.Ser32= (c.96G>C) is associated with Alagille syndrome due to a JAG1 point mutation, tetralogy of fallot, Charcot-Marie-Tooth disease, axonal, Type 2HH (ClinVar).

How common is JAG1 p.Ser32= (c.96G>C) in the general population?

JAG1 p.Ser32= (c.96G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

JAG1 p.Ser32=

c.96G>C · VCV3573237

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -2.4	GERP -0.54
Overall
CADD	10.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Overall 0.000124% 2/1,608,636 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	8.47e-05%	1,180,012

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.Ser32=
Coding: c.96G>C
MANE Select: NM_000214
Type: single nucleotide variant
Location: chr20:10672992 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.02 · 7 PDB

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

Also linked: tetralogy of fallot Charcot-Marie-Tooth disease, axonal, Type 2HH deafness, congenital heart defects, and posterior embryotoxon

Similar variants

JAG1 p.Ser32Ter Pathogenic ★★ same residue
JAG1 p.Ser32Leu 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
JAG1 c.886+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-ser32 (accessed [today's date]).

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