Is ITGB2 p.Arg34Trp (c.100C>T) pathogenic?

ITGB2 p.Arg34Trp (c.100C>T) is classified Uncertain significance in ITGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: likely benign (0.1318); Very rare (popmax 0.00668%, eas); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Arg34Trp (c.100C>T)?

ITGB2 p.Arg34Trp (c.100C>T) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Arg34Trp (c.100C>T) in the general population?

ITGB2 p.Arg34Trp (c.100C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

How is Leukocyte adhesion deficiency inherited?

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

What do computational predictors say about ITGB2 p.Arg34Trp (c.100C>T)?

AlphaMissense predicts likely benign (score 0.1318) — an in-silico prediction, not a clinical call.

ITGB2 p.Arg34Trp

c.100C>T · rs775878305 · VCV1013868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1318 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

leukocyte adhesion deficiency 1

Computational evidence

Protein change
AlphaMissense	0.1318	likely benign
REVEL	0.504	indeterminate
SaProt	LLR -10.69	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -3.9, phastCons 0.62
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.00051 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,892 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000867% 14/1,614,008 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,964
Admixed American	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000424%	236,002

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.Arg34Trp
Coding: c.100C>T
MANE Select: NM_000211
dbSNP: rs775878305
Type: single nucleotide variant
Location: chr21:44910331 (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 34: a disulfide bond; the psi domain; 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.Arg34Gln 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-arg34trp (accessed [today's date]).

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