Is ITGB2 p.Ser59Phe (c.176C>T) pathogenic?

ITGB2 p.Ser59Phe (c.176C>T) is classified Uncertain significance in ITGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-17). AlphaMissense: ambiguous (0.3586); Very rare (popmax 0.00501%, amr); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Ser59Phe (c.176C>T)?

ITGB2 p.Ser59Phe (c.176C>T) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Ser59Phe (c.176C>T) in the general population?

ITGB2 p.Ser59Phe (c.176C>T) is very rare (popmax 0.00501%, amr) (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.Ser59Phe (c.176C>T)?

AlphaMissense predicts ambiguous (score 0.3586) — an in-silico prediction, not a clinical call.

ITGB2 p.Ser59Phe

c.176C>T · rs1038389954 · VCV1510736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3586 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

leukocyte adhesion deficiency 1

Computational evidence

Protein change
AlphaMissense	0.3586	ambiguous
REVEL	0.749	pathogenic-leaning
SaProt	LLR -9.13	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.00051 · regional, not allelic
Overall
CADD	22.7	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 0.00501% Admixed American · 3/59,882 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000311% 5/1,609,180 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,961
Remaining individualsnot grpmax-eligible	0.00161%	62,234
African / African-American	0.00134%	74,866

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.Ser59Phe
Coding: c.176C>T
MANE Select: NM_000211
dbSNP: rs1038389954
Type: single nucleotide variant
Location: chr21:44907067 (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 59: 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.Ser59Thr 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-ser59phe (accessed [today's date]).

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