Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 13 submitters
gnomAD v4.1
Common
common (popmax 92.7%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
leukocyte adhesion deficiency 1
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 · A>T here scores Δ0.48 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.73 | GERP -5, phastCons 0.001 |
| Overall | ||
| CADD | 1.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
92.7%
African / African-American · 69,534/75,038 alleles
Filtering AF
92.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 91.8%
Overall
67.9%
1,095,137/1,612,870 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 92.7% | 1 |
| Middle Eastern | 77.1% | 1 |
| East Asian | 76.8% | 1 |
| Remaining individualsnot grpmax-eligible | 69.2% | 1 |
| Finnishnot grpmax-eligible | 66.8% | 1 |
| European (non-Finnish) | 66.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 66.4% | 2 |
| South Asian | 64.7% | 2 |
| Admixed American | 61% | 2 |
| Amishnot grpmax-eligible | 52% | 2 |
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
- ITGB2
- Protein
- p.Val441=
- Coding
- c.1323T>C
- MANE Select
- NM_000211
- dbSNP
- rs235326
- Type
- single nucleotide variant
- Location
- chr21:44891898 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.02 · 29 PDB
- Residue 441
- a β-strand; a disulfide bond
Disease context
leukocyte adhesion deficiency 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Leukocyte adhesion deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Childhood, Infancy
Similar variants
- ITGB2 p.Val441Ile Uncertain significance ★ ⚠ same residue
- ITGB2 c.741+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ITGB2 c.897+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ITGB2 p.Ala239Thr Pathogenic/Likely pathogenic ★★ same condition
- ITGB2 p.Ala270Val Likely pathogenic ★★ same condition
- ITGB2 p.Arg108Ter Pathogenic/Likely pathogenic ★★ same condition
- ITGB2 p.Arg188Ter Pathogenic ★★ same condition
- ITGB2 p.Arg593Cys Pathogenic ★★ 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/itgb2-p-val441 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown