JAG2 p.Asp592=
c.1776C>T · VCV4822183
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0112%, eas)
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 -0.26 | GERP -3.7 |
| Overall | ||
| CADD | 11.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0112%
East Asian · 5/44,742 alleles
Filtering AF
0.00436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00277%
Overall
0.00236%
38/1,609,654 alleles · ultra-rare
exomes 38/1,457,464 · genomes 0/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0112% | 8,948 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,130 |
| European (non-Finnish) | 0.00246% | 40,653 |
| Admixed American | 0.00167% | 59,836 |
| South Asian | 0.0011% | 90,674 |
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.Asp592=
- Coding
- c.1776C>T
- MANE Select
- NM_002226
- Type
- single nucleotide variant
- Location
- chr14:105149067 (GRCh38)
- Gene constraint
- LOEUF 0.495 · pLI 0.91 (gnomAD)
- Structure
- AlphaFold pLDDT 72.90 · 3 PDB
- Residue 592
- the egf-like 10; atypical domain; a UniProt-annotated variant site (in lgmdr27)
Similar variants
- 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
- JAG2 p.Val1147Met 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-asp592 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown