Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 39.6%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
neutrophil immunodeficiency syndrome
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 -0.36 | GERP -3.8, phastCons 0.015 |
| Overall | ||
| CADD | 8.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
39.6%
African / African-American · 29,519/74,606 alleles
Filtering AF
39.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 39%
Overall
15.6%
252,284/1,612,120 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 39.6% | 3 |
| East Asian | 28.6% | 3 |
| Middle Eastern | 20% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 20% | 5 |
| Remaining individualsnot grpmax-eligible | 18% | 6 |
| Amishnot grpmax-eligible | 15.7% | 6 |
| Finnishnot grpmax-eligible | 14.8% | 7 |
| European (non-Finnish) | 14.1% | 7 |
| Admixed American | 10.8% | 9 |
| South Asian | 10.5% | 9 |
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
- RAC2
- Protein
- p.Ala159=
- Coding
- c.477T>C
- MANE Select
- NM_002872
- dbSNP
- rs1064498
- Type
- single nucleotide variant
- Location
- chr22:37226775 (GRCh38)
- Gene constraint
- LOEUF 0.197 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 93.56 · 4 PDB
- Residue 159
- a binding site; a UniProt-annotated variant site (in imd73c; strong decrease in protein expression); a turn
Disease context
neutrophil immunodeficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Infantile LAD-like disease due to RAC2 deficiency (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
Similar variants
- RAC2 p.Glu62Lys Pathogenic/Likely pathogenic ★★ same condition
- RAC2 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
- RAC2 p.Arg174Trp Uncertain significance ★★ ⚠ same condition
- RAC2 p.Arg183Trp Uncertain significance ★★ ⚠ same condition
- RAC2 p.Arg66His Uncertain significance ★★ ⚠ same condition
- RAC2 p.Arg68Trp Uncertain significance ★★ ⚠ same condition
- RAC2 p.Asp63Asn Uncertain significance ★★ ⚠ same condition
- RAC2 p.Cys18Trp Uncertain significance ★★ ⚠ same condition
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/rac2-p-ala159 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown