Is ITGB2 p.Pro648= (c.1944G>A) pathogenic?

ITGB2 p.Pro648= (c.1944G>A) is classified Conflicting classifications of pathogenicity in ITGB2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-09). Ultra-rare (popmax 0.0201%, eas); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Pro648= (c.1944G>A)?

ITGB2 p.Pro648= (c.1944G>A) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Pro648= (c.1944G>A) in the general population?

ITGB2 p.Pro648= (c.1944G>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

ITGB2 p.Pro648=

c.1944G>A · rs139840790 · VCV898920

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

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 -4.4	GERP -4
Overall
CADD	4.127	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,878 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00838% 135/1,610,878 alleles · ultra-rare exomes 121/1,458,506 · genomes 14/152,372 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,986
South Asian	0.011%	9,109
European (non-Finnish)	0.0089%	11,238
Remaining individualsnot grpmax-eligible	0.008%	12,496
Admixed American	0.00333%	30,015
Finnishnot grpmax-eligible	0.00329%	30,399
African / African-American	0.00266%	37,529

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.Pro648=
Coding: c.1944G>A
MANE Select: NM_000211
dbSNP: rs139840790
Type: single nucleotide variant
Location: chr21:44888829 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.02 · 29 PDB

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 p.Pro648Leu 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-pro648 (accessed [today's date]).

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