ADGRE2 p.Ala734=
c.2202G>A · rs200359297 · VCV2077274
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
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 -15 | GERP -3.7 |
| Overall | ||
| CADD | 3.473 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,062 alleles
Filtering AF
0.0216%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0206%
Overall
0.0188%
304/1,614,126 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,031 |
| European (non-Finnish) | 0.0239% | 4,184 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| South Asian | 0.00549% | 18,216 |
| African / African-American | 0.00533% | 18,760 |
| East Asian | 0.00446% | 22,439 |
| Admixed American | 0.00167% | 60,018 |
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.Ala734=
- Coding
- c.2202G>A
- MANE Select
- NM_013447
- dbSNP
- rs200359297
- Type
- single nucleotide variant
- Location
- chr19:14743766 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.44 · 3 PDB
Similar variants
- ADGRE2 p.Ala734Val Uncertain significance ★★ ⚠ same residue
- 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
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-ala734 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown