Is ITGB2 p.Phe179= (c.537C>T) pathogenic?

ITGB2 p.Phe179= (c.537C>T) is classified Conflicting classifications of pathogenicity in ITGB2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-24). Rare (popmax 0.1%, eas); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Phe179= (c.537C>T)?

ITGB2 p.Phe179= (c.537C>T) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Phe179= (c.537C>T) in the general population?

ITGB2 p.Phe179= (c.537C>T) is rare (popmax 0.1%, eas) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

ITGB2 p.Phe179=

c.537C>T · rs371548080 · VCV340169

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, 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 -3.4	GERP -5
Overall
CADD	1.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,866 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0688%

Overall 0.00893% 144/1,613,224 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	997
South Asian	0.0615%	1,626
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Middle Eastern	0.0165%	6,060
Admixed American	0.00666%	15,006
African / African-American	0.004%	25,011
European (non-Finnish)	0.00195%	51,268

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.Phe179=
Coding: c.537C>T
MANE Select: NM_000211
dbSNP: rs371548080
Type: single nucleotide variant
Location: chr21:44901696 (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 179: a turn; a disulfide bond; the vwfa 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.Phe179fs Pathogenic ★ 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-phe179 (accessed [today's date]).

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