ADGRB2 p.Pro1577=
c.4731G>A · VCV3709574
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0562%, afr)
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 -7.9 | GERP -3.2 |
| Overall | ||
| CADD | 0.725 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0562%
African / African-American · 41/72,948 alleles
Filtering AF
0.0425%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00397%
63/1,587,998 alleles · ultra-rare
exomes 49/1,435,716 · genomes 14/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0562% | 1,779 |
| Remaining individualsnot grpmax-eligible | 0.00816% | 12,261 |
| Admixed American | 0.00583% | 17,151 |
| East Asian | 0.00229% | 43,598 |
| Finnishnot grpmax-eligible | 0.00157% | 63,830 |
| European (non-Finnish) | 0.00102% | 97,714 |
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.Pro1577=
- Coding
- c.4731G>A
- MANE Select
- NM_001364857
- Type
- single nucleotide variant
- Location
- chr1:31727447 (GRCh38)
- Gene constraint
- LOEUF 0.383 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.10 · 1 PDB
- Residue 1577
- the 'disordered' region
Similar variants
- ADGRB2 p.Pro1577Leu Benign ★★ same residue
- 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
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-pro1577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown