Is ITGA2B p.Phe191Val (c.571T>G) pathogenic?

ITGA2B p.Phe191Val (c.571T>G) is classified Likely pathogenic in ITGA2B (ClinVar, Expert panel, 1 submitter; last evaluated 2023-11-02). AlphaMissense: likely benign (0.2682); Absent from gnomAD v4.1; Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Phe191Val (c.571T>G)?

ITGA2B p.Phe191Val (c.571T>G) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Phe191Val (c.571T>G) in the general population?

ITGA2B p.Phe191Val (c.571T>G) 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.Phe191Val (c.571T>G)?

AlphaMissense predicts likely benign (score 0.2682) — an in-silico prediction, not a clinical call.

ITGA2B p.Phe191Val

c.571T>G · rs2048639566 · VCV996171

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2682 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

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

PM2_Supporting PP4_Strong PM4

Curation rationale (ClinGen, verbatim)

The NM_000419.5(ITGA2B):c.571T>G (p.Phe191Val) variant has been reported in at least 1 compound heterozygous GT proband (PMID:25728920) with a phenotype highly specific to Glanzmann thrombasthenia with mucocutaneous bleeding, impaired aggregation with all agonists except ristocetin, and reduced surface expression of αIIbβ3 measured by flow cytometry (PP4_Strong). It is absent from population databases, including gnomADv2.1.1 (PM2_supporting). Splicing predictors, HSF and SpliceAI, agree that there is activation of a cryptic donor site with potential alteration of splicing. This was confirmed by minigene study in PMID: 20020534; sequencing revealed the most common transcript contained a 4-bp deletion that introduced a frameshift and a premature stop codon in exon 7 of 30 (PM4). In summary, this variant meets criteria to be classified as likely pathogenic for GT. GT-specific criteria applied: PM2_Supporting, PM4, and PP4_Strong.

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

Computational evidence

Protein change
AlphaMissense	0.2682	likely benign ⚠ discordant with ClinVar
REVEL	0.165	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.90	donor gain · deltas
Pangolin	Δ0.71	gain · loss 0.39 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 0.71, phastCons 0.004
Regional constraint	o/e 1.02	unconstrained · MANE · 4,459 bp · p 0.74 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGA2B
Protein: p.Phe191Val
Coding: c.571T>G
MANE Select: NM_000419
dbSNP: rs2048639566
Type: single nucleotide variant
Location: chr17:44385554 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 191: a turn; 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 p.Phe191_Ser192insArgThr Pathogenic ★★★ same residue
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

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-phe191val (accessed [today's date]).

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