Is ITGB2 p.Pro109= (c.327A>G) pathogenic?

ITGB2 p.Pro109= (c.327A>G) is classified Uncertain significance in ITGB2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-12-21). Ultra-rare (popmax 0.0329%, mid); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Pro109= (c.327A>G)?

ITGB2 p.Pro109= (c.327A>G) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Pro109= (c.327A>G) in the general population?

ITGB2 p.Pro109= (c.327A>G) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ITGB2 p.Pro109=

c.327A>G · rs199932521 · VCV847665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

leukocyte adhesion deficiency 1

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 1.8	GERP 0.36, phastCons 1
Overall
CADD	17.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.00582% 94/1,614,070 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
South Asian	0.0132%	7,591
European (non-Finnish)	0.00636%	15,734
Admixed American	0.005%	20,003
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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.Pro109=
Coding: c.327A>G
MANE Select: NM_000211
dbSNP: rs199932521
Type: single nucleotide variant
Location: chr21:44906916 (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 109: a disulfide bond; a β-strand

Full ITGB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

leukocyte adhesion deficiency 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leukocyte adhesion deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

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
ITGB2 p.Asp128Asn Pathogenic/Likely 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-pro109 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown