Is ITGB2 p.Ser730= (c.2190C>T) pathogenic?

ITGB2 p.Ser730= (c.2190C>T) is classified Likely benign in ITGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). Ultra-rare (popmax 0.0164%, mid); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Ser730= (c.2190C>T)?

ITGB2 p.Ser730= (c.2190C>T) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Ser730= (c.2190C>T) in the general population?

ITGB2 p.Ser730= (c.2190C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

ITGB2 p.Ser730=

c.2190C>T · rs375930896 · VCV2194760

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, 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 -1.4	GERP -4.8
Overall
CADD	4.808	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.00186% 30/1,613,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00668%	14,980
East Asian	0.00223%	44,890
Finnishnot grpmax-eligible	0.00157%	63,860
European (non-Finnish)	0.00119%	84,287
South Asian	0.0011%	91,084

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.Ser730=
Coding: c.2190C>T
MANE Select: NM_000211
dbSNP: rs375930896
Type: single nucleotide variant
Location: chr21:44886793 (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 730: an α-helix

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.Ser730Asn Likely benign ★★ 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-ser730 (accessed [today's date]).

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