ADGRA2 p.Leu89=
c.267G>C · VCV3834812
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 2.8 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 8.37 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,078 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00174%
28/1,609,734 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,078 |
| Admixed American | 0.00833% | 11,999 |
| African / African-American | 0.00267% | 37,433 |
| European (non-Finnish) | 0.00162% | 61,900 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,318 |
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
- ADGRA2
- Protein
- p.Leu89=
- Coding
- c.267G>C
- MANE Select
- NM_032777
- Type
- single nucleotide variant
- Location
- chr8:37814896 (GRCh38)
- Gene constraint
- LOEUF 0.943 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.47
Similar variants
- ADGRA2 c.1608+5T>C Benign ★★ same type
- ADGRA2 p.Ala681Thr Benign ★★ ⚠ same type
- ADGRA2 p.Arg671= Benign ★★ same type
- ADGRA2 p.Ala1082Ser Uncertain significance ★ ⚠ same type
- ADGRA2 p.Ala1094Ser Uncertain significance ★ ⚠ same type
- ADGRA2 p.Ala1098Val Uncertain significance ★ ⚠ same type
- ADGRA2 p.Ala1102Thr Uncertain significance ★ ⚠ same type
- ADGRA2 p.Ala1102Val 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/adgra2-p-leu89 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown