Is JAG1 p.Ser41= (c.123C>T) pathogenic?

JAG1 p.Ser41= (c.123C>T) is classified Likely benign in JAG1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-04). Very rare (popmax 0.0022%, sas); Associated with Alagille syndrome due to a JAG1 point mutation.

What condition is associated with JAG1 p.Ser41= (c.123C>T)?

JAG1 p.Ser41= (c.123C>T) is associated with Alagille syndrome due to a JAG1 point mutation (ClinVar).

How common is JAG1 p.Ser41= (c.123C>T) in the general population?

JAG1 p.Ser41= (c.123C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

JAG1 p.Ser41=

c.123C>T · rs761894056 · VCV1576158

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, 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 0.55	GERP -2.7, phastCons 0.99
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,090 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000496% 8/1,612,198 alleles · very rare exomes 8/1,459,898 · genomes 0/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,545
European (non-Finnish)	0.000508%	196,671

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.Ser41=
Coding: c.123C>T
MANE Select: NM_000214
dbSNP: rs761894056
Type: single nucleotide variant
Location: chr20:10672965 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 73.02 · 7 PDB
Residue 41: a β-strand

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-ser41 (accessed [today's date]).

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