ARRB2 p.Leu288=
c.864C>T · rs34750256 · VCV715690
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.05%, 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 -4.6 | GERP -3.9 |
| Overall | ||
| CADD | 5.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.05%
African / African-American · 785/75,046 alleles
Filtering AF
0.985%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.961%
Overall
0.0771%
1,245/1,614,188 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.05% | 96 |
| Middle Eastern | 0.28% | 357 |
| Admixed American | 0.122% | 822 |
| Remaining individualsnot grpmax-eligible | 0.106% | 947 |
| European (non-Finnish) | 0.0249% | 4,014 |
| Finnishnot grpmax-eligible | 0.00781% | 12,807 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| South Asian | 0.00329% | 30,362 |
| East Asian | 0.00223% | 44,876 |
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
- ARRB2
- Protein
- p.Leu288=
- Coding
- c.864C>T
- MANE Select
- NM_004313
- dbSNP
- rs34750256
- Type
- single nucleotide variant
- Location
- chr17:4719367 (GRCh38)
- Gene constraint
- LOEUF 0.562 · pLI 0.60 (gnomAD)
- Structure
- AlphaFold pLDDT 83.97 · 1 PDB
- Residue 288
- the 'interaction with traf6' region
Similar variants
- ARRB2 p.Ile82= Benign ★★ same type
- ARRB2 p.Ala362Thr Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg100Cys Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg148Gln Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg189Cys Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg196Gln Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg26Gln Uncertain significance ★ ⚠ same type
- ARRB2 p.Arg283Trp 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/arrb2-p-leu288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown