Is ITGB2 p.Ser39= (c.117G>A) pathogenic?

ITGB2 p.Ser39= (c.117G>A) is classified Benign/Likely benign in ITGB2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.42%, sas); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Ser39= (c.117G>A)?

ITGB2 p.Ser39= (c.117G>A) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Ser39= (c.117G>A) in the general population?

ITGB2 p.Ser39= (c.117G>A) is low-frequency (popmax 4.42%, sas) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

ITGB2 p.Ser39=

c.117G>A · rs35903905 · VCV340180

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.42%, 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 -6.5	GERP -4.1
Overall
CADD	4.522	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.42% South Asian · 4,028/91,082 alleles

Filtering AF 4.31% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.26%

Overall 1.59% 25,652/1,614,098 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.42%	23
East Asian	3.67%	27
Middle Eastern	2.18%	46
Remaining individualsnot grpmax-eligible	1.71%	59
Finnishnot grpmax-eligible	1.61%	62
European (non-Finnish)	1.4%	71
Ashkenazi Jewishnot grpmax-eligible	1.35%	74
Admixed American	1.1%	91
Amishnot grpmax-eligible	0.987%	101
African / African-American	0.229%	436

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.Ser39=
Coding: c.117G>A
MANE Select: NM_000211
dbSNP: rs35903905
Type: single nucleotide variant
Location: chr21:44910314 (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 39: the psi 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.Ser39Leu Uncertain significance ★★ ⚠ same residue
ITGB2 p.Ser39fs Pathogenic/Likely 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

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-ser39 (accessed [today's date]).

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