Is ITGB2 p.Arg595Trp (c.1783C>T) pathogenic?

ITGB2 p.Arg595Trp (c.1783C>T) is classified Uncertain significance in ITGB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). AlphaMissense: likely benign (0.1229); Ultra-rare (popmax 0.0461%, sas); Associated with Inborn genetic diseases.

What condition is associated with ITGB2 p.Arg595Trp (c.1783C>T)?

ITGB2 p.Arg595Trp (c.1783C>T) is associated with Inborn genetic diseases, leukocyte adhesion deficiency 1 (ClinVar).

How common is ITGB2 p.Arg595Trp (c.1783C>T) in the general population?

ITGB2 p.Arg595Trp (c.1783C>T) is ultra-rare (popmax 0.0461%, sas) (gnomAD).

What do computational predictors say about ITGB2 p.Arg595Trp (c.1783C>T)?

AlphaMissense predicts likely benign (score 0.1229) — an in-silico prediction, not a clinical call.

ITGB2 p.Arg595Trp

c.1783C>T · rs756086891 · VCV2591613

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1229 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0461%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1229	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -4.6, phastCons 0.93
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.00051 · regional, not allelic
Overall
CADD	21.7	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 0.0461% South Asian · 42/91,080 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0311%

Overall 0.00409% 66/1,612,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0461%	2,169
East Asian	0.00446%	22,437
Remaining individualsnot grpmax-eligible	0.0032%	31,230
African / African-American	0.00267%	37,436
European (non-Finnish)	0.00153%	65,549

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.Arg595Trp
Coding: c.1783C>T
MANE Select: NM_000211
dbSNP: rs756086891
Type: single nucleotide variant
Location: chr21:44889370 (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 595: the i-egf 4 domain; a β-strand

Full ITGB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: leukocyte adhesion deficiency 1

Similar variants

ITGB2 p.Arg595Gln 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-arg595trp (accessed [today's date]).

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