Is JAG2 p.Ser367= (c.1101C>T) pathogenic?

JAG2 p.Ser367= (c.1101C>T) is classified Likely benign in JAG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-07-26). Ultra-rare (popmax 0.0164%, mid); Associated with JAG2-related disorder.

What condition is associated with JAG2 p.Ser367= (c.1101C>T)?

JAG2 p.Ser367= (c.1101C>T) is associated with JAG2-related disorder (ClinVar).

How common is JAG2 p.Ser367= (c.1101C>T) in the general population?

JAG2 p.Ser367= (c.1101C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

JAG2 p.Ser367=

c.1101C>T · rs768876569 · VCV3032910

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

JAG2-related disorder

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 -16	GERP -4.4
Overall
CADD	1.784	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00973%

Overall 0.00956% 154/1,611,274 alleles · ultra-rare exomes 152/1,459,030 · genomes 2/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Remaining individualsnot grpmax-eligible	0.0128%	7,800
European (non-Finnish)	0.012%	8,365
South Asian	0.00331%	30,211
Finnishnot grpmax-eligible	0.00159%	62,700

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: JAG2
Protein: p.Ser367=
Coding: c.1101C>T
MANE Select: NM_002226
dbSNP: rs768876569
Type: single nucleotide variant
Location: chr14:105151678 (GRCh38)
Gene constraint: LOEUF 0.495 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 72.90 · 3 PDB
Residue 367: a UniProt-annotated variant site (in lgmdr27); the egf-like 4 domain

Full JAG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

JAG2-related disorder

Similar variants

JAG2 p.Ser367Tyr Uncertain significance ★ ⚠ same residue
JAG2 p.Arg979Cys Uncertain significance ★★ ⚠ same condition
JAG2 p.Gly530Arg Uncertain significance ★ ⚠ same condition
JAG2 p.Val1103Leu Uncertain significance ★ ⚠ same condition
JAG2 c.1382-6C>T Likely benign same condition
JAG2 c.1429-6G>A Likely benign same condition
JAG2 c.1429-7C>T Likely benign same condition
JAG2 c.1603-7C>T Likely benign 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/jag2-p-ser367 (accessed [today's date]).

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