Is ITGB2 p.Phe464Val (c.1390T>G) pathogenic?

ITGB2 p.Phe464Val (c.1390T>G) is classified Uncertain significance in ITGB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-23). AlphaMissense: likely benign (0.0983); Very rare (popmax 8.47e-05%, nfe); Associated with leukocyte adhesion deficiency 1.

What condition is associated with ITGB2 p.Phe464Val (c.1390T>G)?

ITGB2 p.Phe464Val (c.1390T>G) is associated with leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Phe464Val (c.1390T>G) in the general population?

ITGB2 p.Phe464Val (c.1390T>G) is very rare (popmax 8.47e-05%, nfe) (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.Phe464Val (c.1390T>G)?

AlphaMissense predicts likely benign (score 0.0983) — an in-silico prediction, not a clinical call.

ITGB2 p.Phe464Val

c.1390T>G · rs1601287199 · VCV646024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0983 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

leukocyte adhesion deficiency 1

Computational evidence

Protein change
AlphaMissense	0.0983	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -2.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.14	GERP -5
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.00051 · regional, not allelic
Overall
CADD	7.855	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,972 alleles

Overall 6.87e-05% 1/1,456,164 alleles · very rare

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.Phe464Val
Coding: c.1390T>G
MANE Select: NM_000211
dbSNP: rs1601287199
Type: single nucleotide variant
Location: chr21:44891831 (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 464: a β-strand; a disulfide bond; the i-egf 1 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.Phe464Leu 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-phe464val (accessed [today's date]).

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