Is JAG2 p.Gly467Glu (c.1400G>A) pathogenic?

JAG2 p.Gly467Glu (c.1400G>A) is classified Uncertain significance in JAG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely benign (0.2213); Ultra-rare (popmax 0.0212%, amr).

How common is JAG2 p.Gly467Glu (c.1400G>A) in the general population?

JAG2 p.Gly467Glu (c.1400G>A) is ultra-rare (popmax 0.0212%, amr) (gnomAD).

What do computational predictors say about JAG2 p.Gly467Glu (c.1400G>A)?

AlphaMissense predicts likely benign (score 0.2213) — an in-silico prediction, not a clinical call.

JAG2 p.Gly467Glu

c.1400G>A · rs757195573 · VCV2388352

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2213 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0212%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2213	likely benign
REVEL	0.692	pathogenic-leaning
SaProt	LLR -7.80	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 22 kb · p 3.9e-21 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0212% Admixed American · 12/56,728 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00956%

Overall 0.000754% 12/1,590,978 alleles · ultra-rare exomes 12/1,438,700 · genomes 0/152,278 · 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: JAG2
Protein: p.Gly467Glu
Coding: c.1400G>A
MANE Select: NM_002226
dbSNP: rs757195573
Type: single nucleotide variant
Location: chr14:105150893 (GRCh38)
Gene constraint: LOEUF 0.495 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 72.90 · 3 PDB
Residue 467: the egf-like 7; calcium-binding domain; a UniProt-annotated variant site (in lgmdr27)

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

Similar variants

JAG2 p.Gly467Arg Uncertain significance ★ ⚠ same residue
JAG2 p.Gly839Arg Likely pathogenic ★★ same type
JAG2 p.Arg466His Uncertain significance ★★ ⚠ same type
JAG2 p.Arg686His Uncertain significance ★★ ⚠ same type
JAG2 p.Arg979Cys Uncertain significance ★★ ⚠ same type
JAG2 p.Gly994Arg Uncertain significance ★★ ⚠ same type
JAG2 p.Pro1130Leu Uncertain significance ★★ ⚠ same type
JAG2 p.Pro157Leu Uncertain significance ★★ ⚠ same type

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-gly467glu (accessed [today's date]).

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