ADGRB2 p.Cys512=
c.1536C>T · VCV3835212
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.27 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.6 | GERP -4.2 |
| Overall | ||
| CADD | 2.128 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,028 alleles
Filtering AF
0.0044%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00314%
Overall
0.00199%
29/1,454,010 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,028 |
| East Asian | 0.0112% | 8,945 |
| South Asian | 0.00886% | 11,291 |
| Remaining individualsnot grpmax-eligible | 0.00644% | 15,519 |
| European (non-Finnish) | 0.000936% | 106,804 |
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
- ADGRB2
- Protein
- p.Cys512=
- Coding
- c.1536C>T
- MANE Select
- NM_001364857
- Type
- single nucleotide variant
- Location
- chr1:31741849 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.10 · 1 PDB
- Residue 512
- the tsp type-1 4 domain; a disulfide bond
Similar variants
- ADGRB2 p.Ala117Val Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala1193Thr Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala1193Val Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala1411Val Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala36Thr Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala733Thr Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Ala901Thr Uncertain significance ★★ ⚠ same type
- ADGRB2 p.Arg1105Cys 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/adgrb2-p-cys512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown