Is ITGB2 p.Arg71Ser (c.213G>C) pathogenic?

ITGB2 p.Arg71Ser (c.213G>C) is classified Uncertain significance in ITGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-04). AlphaMissense: ambiguous (0.4757); Very rare (popmax 0.00534%, afr); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Arg71Ser (c.213G>C)?

ITGB2 p.Arg71Ser (c.213G>C) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Arg71Ser (c.213G>C) in the general population?

ITGB2 p.Arg71Ser (c.213G>C) is very rare (popmax 0.00534%, afr) (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.Arg71Ser (c.213G>C)?

AlphaMissense predicts ambiguous (score 0.4757) — an in-silico prediction, not a clinical call.

ITGB2 p.Arg71Ser

c.213G>C · rs371854500 · VCV1424290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

leukocyte adhesion deficiency 1

Computational evidence

Protein change
AlphaMissense	0.4757	ambiguous
REVEL	0.593	indeterminate
SaProt	LLR -10.12	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -1.2
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.00051 · regional, not allelic
Overall
CADD	17.05	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 0.00534% African / African-American · 4/74,928 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000806% 13/1,613,686 alleles · very rare exomes 10/1,461,474 · genomes 3/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,732
Admixed American	0.005%	20,002
European (non-Finnish)	0.000509%	196,619

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.Arg71Ser
Coding: c.213G>C
MANE Select: NM_000211
dbSNP: rs371854500
Type: single nucleotide variant
Location: chr21:44907030 (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 71: 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 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
ITGB2 p.Asp128Asn Pathogenic/Likely 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-arg71ser (accessed [today's date]).

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