Is ITGA2B p.Pro772Arg (c.2315C>G) pathogenic?

ITGA2B p.Pro772Arg (c.2315C>G) is classified Uncertain significance in ITGA2B (ClinVar, Expert panel, 4 submitters; last evaluated 2023-01-17). AlphaMissense: likely benign (0.0977); Ultra-rare (popmax 0.0242%, sas); Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Pro772Arg (c.2315C>G)?

ITGA2B p.Pro772Arg (c.2315C>G) is associated with Glanzmann thrombasthenia, Glanzmann thrombasthenia 1 (ClinVar).

How common is ITGA2B p.Pro772Arg (c.2315C>G) in the general population?

ITGA2B p.Pro772Arg (c.2315C>G) is ultra-rare (popmax 0.0242%, sas) (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.Pro772Arg (c.2315C>G)?

AlphaMissense predicts likely benign (score 0.0977) — an in-silico prediction, not a clinical call.

ITGA2B p.Pro772Arg

c.2315C>G · rs531356248 · VCV2498355

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0242%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

Uncertain Significance for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):

PP4_Moderate

Curation rationale (ClinGen, verbatim)

The NM_000419.5(ITGA2B):c.2315C>G (p.Pro772Arg) missense variant has been reported in at least one patient (Patient 7 in PMID:19172520/GT database record 164) who displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia (PP4_moderate). Additionally, αIIbβ3 surface expression was reduced to <10%, as measured by flow cytometry. In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_Moderate (VCEP specifications version 2.1).

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

Computational evidence

Protein change
AlphaMissense	0.0977	likely benign
REVEL	0.321	indeterminate
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.083, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.0004 · regional, not allelic
Overall
CADD	22.6	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 0.0242% South Asian · 22/91,078 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0138%

Overall 0.00173% 28/1,614,182 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0242%	4,140
Finnishnot grpmax-eligible	0.00468%	21,346
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000169%	590,023

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.Pro772Arg
Coding: c.2315C>G
MANE Select: NM_000419
dbSNP: rs531356248
Type: single nucleotide variant
Location: chr17:44376341 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 772: a β-strand

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

Also linked: Glanzmann thrombasthenia 1

For Glanzmann thrombasthenia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ITGA2B p.Pro772Leu Uncertain significance ★★ ⚠ same residue
ITGA2B p.Pro772= Likely benign ★★ 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

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-pro772arg (accessed [today's date]).

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