Is ITGB2 p.Arg488= (c.1464G>A) pathogenic?

ITGB2 p.Arg488= (c.1464G>A) is classified Conflicting classifications of pathogenicity in ITGB2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-13). Rare (popmax 0.242%, sas); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Arg488= (c.1464G>A)?

ITGB2 p.Arg488= (c.1464G>A) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Arg488= (c.1464G>A) in the general population?

ITGB2 p.Arg488= (c.1464G>A) is rare (popmax 0.242%, sas) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

ITGB2 p.Arg488=

c.1464G>A · rs202051683 · VCV340152

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.242%, sas)

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 -4.7
Overall
CADD	3.624	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.242% South Asian · 220/91,080 alleles

Filtering AF 0.215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.205%

Overall 0.0145% 234/1,613,292 alleles · rare exomes 223/1,461,028 · genomes 11/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.242%	414
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.016%	6,250
African / African-American	0.00133%	75,044
European (non-Finnish)	8.47e-05%	1,180,013

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.Arg488=
Coding: c.1464G>A
MANE Select: NM_000211
dbSNP: rs202051683
Type: single nucleotide variant
Location: chr21:44890171 (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 488: the i-egf 2 domain

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.Arg488Trp Uncertain significance ★ ⚠ same residue
ITGB2 p.Arg488Gln 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

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-arg488 (accessed [today's date]).

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