Is ITGA2B p.Arg196= (c.588T>C) pathogenic?

ITGA2B p.Arg196= (c.588T>C) is classified Likely benign in ITGA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). Very rare (popmax 6.85e-05%); Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Arg196= (c.588T>C)?

ITGA2B p.Arg196= (c.588T>C) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Arg196= (c.588T>C) in the general population?

ITGA2B p.Arg196= (c.588T>C) is very rare (popmax 6.85e-05%) (gnomAD).

How is Glanzmann thrombasthenia inherited?

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

ITGA2B p.Arg196=

c.588T>C · rs1255308679 · VCV3014566

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Conditions

Glanzmann thrombasthenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.045	GERP -3.4, phastCons 0.4
Overall
CADD	9.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,459,638 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: ITGA2B
Protein: p.Arg196=
Coding: c.588T>C
MANE Select: NM_000419
dbSNP: rs1255308679
Type: single nucleotide variant
Location: chr17:44385322 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 196: an α-helix; a disulfide bond

Full ITGA2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Glanzmann thrombasthenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glanzmann thrombasthenia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ITGA2B c.1210+105A>G Likely pathogenic ★★★ same condition
ITGA2B c.1210+5G>A Likely pathogenic ★★★ same condition
ITGA2B c.1211-1G>C Likely pathogenic ★★★ same condition
ITGA2B c.1544+1G>A Pathogenic ★★★ same condition
ITGA2B c.1545-1G>A Pathogenic ★★★ same condition
ITGA2B c.1600+1G>A Pathogenic ★★★ same condition
ITGA2B c.1752+2T>C Pathogenic ★★★ same condition
ITGA2B c.1753-1G>A 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/itga2b-p-arg196 (accessed [today's date]).

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