Is ITGB3 p.Pro294= (c.882T>C) pathogenic?

ITGB3 p.Pro294= (c.882T>C) is classified Benign in ITGB3 (ClinVar, Expert panel, 8 submitters; last evaluated 2022-12-01). Common (popmax 22.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Glanzmann thrombasthenia.

What condition is associated with ITGB3 p.Pro294= (c.882T>C)?

ITGB3 p.Pro294= (c.882T>C) is associated with Glanzmann thrombasthenia (ClinVar).

How is Glanzmann thrombasthenia inherited?

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

ITGB3 p.Pro294=

Q: How common is ITGB3 p.Pro294= (c.882T>C) in the general population?

ITGB3 p.Pro294= (c.882T>C) is common (popmax 22.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.882T>C · rs5919 · VCV255541

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 22.3%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

Benign for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):

BP7 BP4 BA1

Curation rationale (ClinGen, verbatim)

After a comprehensive literature search of the synonymous variant NM_000212.3(ITGB3):c.882T>C (p.Pro294=), no individuals with Glanzmann thrombasthenia were reported with the variant. Moreover, the variant has a minor allele frequency of 0.2463 (4912/19940 alleles) in gnomAD, found in the East Asian population, which is considerably higher than the expected frequency of the disease (BA1). In Silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing at a nucleotide site that is not highly conserved. In conclusion the criteria BA1, BP4, and BP7 were applied to reach a classification of benign.

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

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 0.43	GERP -1.7, phastCons 0.99
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.3% East Asian · 10,008/44,860 alleles

Filtering AF 21.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 21.8%

Overall 8.26% 133,261/1,613,828 alleles · common exomes 117,232/1,461,626 · genomes 16,029/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	22.3%	4
Middle Eastern	17.4%	6
South Asian	16%	6
African / African-American	15.7%	6
Amishnot grpmax-eligible	14.6%	7
Ashkenazi Jewishnot grpmax-eligible	13.9%	7
Remaining individualsnot grpmax-eligible	9.99%	10
Admixed American	6.81%	15
European (non-Finnish)	6.67%	15
Finnishnot grpmax-eligible	4.06%	25

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: ITGB3
Protein: p.Pro294=
Coding: c.882T>C
MANE Select: NM_000212
dbSNP: rs5919
Type: single nucleotide variant
Location: chr17:47287174 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 87.19 · 125 PDB
Residue 294: the 'cx3cl1-binding' region; an α-helix; the vwfa domain

Full ITGB3 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

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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/itgb3-p-pro294 (accessed [today's date]).

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