ADGRE2 p.Pro399=
c.1197T>G · rs140888899 · VCV714764
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.968%, afr)
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 -0.68 | GERP -3.1, phastCons 0.017 |
| Overall | ||
| CADD | 1.155 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.968%
African / African-American · 726/75,030 alleles
Filtering AF
0.909%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.886%
Overall
0.0511%
824/1,613,428 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.968% | 103 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,784 |
| Admixed American | 0.0534% | 1,874 |
| Middle Eastern | 0.0517% | 1,935 |
| European (non-Finnish) | 0.00237% | 42,133 |
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
- ADGRE2
- Protein
- p.Pro399=
- Coding
- c.1197T>G
- MANE Select
- NM_013447
- dbSNP
- rs140888899
- Type
- single nucleotide variant
- Location
- chr19:14755873 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.44 · 3 PDB
- Residue 399
- the gain-b domain
Similar variants
- ADGRE2 p.Ala359Gly Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala44Thr Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala554Val Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala555Ser Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala589Thr Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala603Thr Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala656Thr Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala664Gly 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/adgre2-p-pro399 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown