Is ITGA2B p.Val934Phe (c.2800G>T) pathogenic?

ITGA2B p.Val934Phe (c.2800G>T) is classified Likely pathogenic in ITGA2B (ClinVar, Expert panel, 1 submitter; last evaluated 2024-06-06). AlphaMissense: ambiguous (0.4333); Absent from gnomAD v4.1; Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Val934Phe (c.2800G>T)?

ITGA2B p.Val934Phe (c.2800G>T) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Val934Phe (c.2800G>T) in the general population?

ITGA2B p.Val934Phe (c.2800G>T) is absent from gnomAD v4.1 (gnomAD).

How is Glanzmann thrombasthenia inherited?

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

What do computational predictors say about ITGA2B p.Val934Phe (c.2800G>T)?

AlphaMissense predicts ambiguous (score 0.4333) — an in-silico prediction, not a clinical call.

ITGA2B p.Val934Phe

c.2800G>T · rs77458039 · VCV996165

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4333 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,545,916)

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

Likely Pathogenic for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):

PM2_Supporting PS3_Supporting PP4_Strong PM3

Curation rationale (ClinGen, verbatim)

The ITGA2B missense variant NM_000419.5:c.2800G>T replaces the valine residue with a phenylalanine residue (p.Val934Phe). All requirements for PP4 at an upgraded strength of strong (PP4_Strong) are met by proband GT20 (PMID 25728920): epistaxis; absent platelet aggregation in response to physiologic agonists except normal response to ristocetin; flow cytometry showed 10-20% expression of αIIbβ3; direct sequencing of all exons and splice sites of ITGA2B and ITGB3, as well as upstream regions. This variant has also been observed in a homozygous proband (PMID: 34347927) and a proband (PMID: 25728920) who also harbors a second ITGA2B variant (c.1413C>G, p.Tyr471Ter) previously classified by the VCEP as pathogenic (phase unconfirmed) (PM3). Furthermore, this variant has not been observed in population databases (absent from gnomAD v4.1.0; PM2_supporting). Finally, a functional study of this variant has been reported (PMID: 20020534; flow cytometric detection of αIIb, β3, and αIIbβ3 positive cells following transient transfection of ITGA2B cDNA carrying this variant), finding approximately 20% positive cells for the β3 subunit compared to WT (PS3_supporting). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PS3_supporting, PM2_supporting, PM3, and PP4_strong.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.4333	ambiguous
REVEL	0.46	indeterminate
SaProt	LLR -11.32	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.0004 · regional, not allelic
Overall
CADD	23.4	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

No allele count reported in gnomAD v4.1 (AN 1,545,916). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ITGA2B
Protein: p.Val934Phe
Coding: c.2800G>T
MANE Select: NM_000419
dbSNP: rs77458039
Type: single nucleotide variant
Location: chr17:44375039 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 934: a β-strand; a UniProt-annotated variant site (in gt1; severe type 1 phenotype; the mutation prevented normal itga2b/itgb3 complex expression on the cell surface)

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-val934phe (accessed [today's date]).

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