ADGRE5 p.Pro266=
c.798G>A · rs752522386 · VCV2649420
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0852%, 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 -1.7 | |
| Overall | ||
| CADD | 5.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0852%
Middle Eastern · 4/4,696 alleles
Filtering AF
0.029%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0175%
Overall
0.00435%
57/1,311,622 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0852% | 1,174 |
| Remaining individualsnot grpmax-eligible | 0.0114% | 8,762 |
| Admixed American | 0.00888% | 11,264 |
| European (non-Finnish) | 0.00397% | 25,206 |
| South Asian | 0.00263% | 38,047 |
| East Asian | 0.00253% | 39,586 |
| Finnishnot grpmax-eligible | 0.00185% | 54,078 |
| African / African-American | 0.00181% | 55,350 |
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
- ADGRE5
- Protein
- p.Pro266=
- Coding
- c.798G>A
- MANE Select
- NM_078481
- dbSNP
- rs752522386
- Type
- single nucleotide variant
- Location
- chr19:14397914 (GRCh38)
- Gene constraint
- LOEUF 0.973 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.39 · 9 PDB
Similar variants
- ADGRE5 p.Pro266Leu Likely benign ★ same residue
- ADGRE5 c.1183+10G>A Benign ★★ same type
- ADGRE5 p.Asn371= Benign ★★ same type
- ADGRE5 p.Ile666Met Likely benign ★★ ⚠ same type
- ADGRE5 p.Leu635= Benign ★★ same type
- ADGRE5 p.Ala379Thr Uncertain significance ★ ⚠ same type
- ADGRE5 p.Ala388Ser Uncertain significance ★ ⚠ same type
- ADGRE5 p.Ala39Thr 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/adgre5-p-pro266 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown