JAG2 p.Ser509=
c.1527C>T · VCV4923426
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0415%, nfe)
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 -4.3 | GERP -3.9 |
| Overall | ||
| CADD | 5.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0415%
European (non-Finnish) · 477/1,148,050 alleles
Filtering AF
0.0384%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0372%
Overall
0.0329%
511/1,552,168 alleles · ultra-rare
exomes 475/1,399,998 · genomes 36/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0415% | 2,407 |
| Remaining individualsnot grpmax-eligible | 0.0366% | 2,734 |
| African / African-American | 0.00684% | 14,625 |
| South Asian | 0.00593% | 16,855 |
| Admixed American | 0.00391% | 25,607 |
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.Ser509=
- Coding
- c.1527C>T
- MANE Select
- NM_002226
- Type
- single nucleotide variant
- Location
- chr14:105150679 (GRCh38)
- Gene constraint
- LOEUF 0.495 · pLI 0.91 (gnomAD)
- Structure
- AlphaFold pLDDT 72.90 · 3 PDB
- Residue 509
- the egf-like 8 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-ser509 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown