ADGRE2 p.Ala554=
c.1662G>A · rs139102333 · VCV1935644
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.074 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.4 |
| Overall | ||
| CADD | 7.523 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,084 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00062%
10/1,613,894 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,084 |
| Admixed American | 0.005% | 19,990 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| South Asian | 0.0011% | 91,070 |
| European (non-Finnish) | 0.000339% | 295,001 |
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.Ala554=
- Coding
- c.1662G>A
- MANE Select
- NM_013447
- dbSNP
- rs139102333
- Type
- single nucleotide variant
- Location
- chr19:14752455 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.44 · 3 PDB
Similar variants
- ADGRE2 p.Ala554Val Uncertain significance ★★ ⚠ same residue
- ADGRE2 p.Ala359Gly Uncertain significance ★★ ⚠ same type
- ADGRE2 p.Ala44Thr 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-ala554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown