Is ITGA2B p.Pro230= (c.690A>C) pathogenic?

ITGA2B p.Pro230= (c.690A>C) is classified Likely benign in ITGA2B (ClinVar, Expert panel, 2 submitters; last evaluated 2023-08-15). Ultra-rare (popmax 0.01%, amr); Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Pro230= (c.690A>C)?

ITGA2B p.Pro230= (c.690A>C) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Pro230= (c.690A>C) in the general population?

ITGA2B p.Pro230= (c.690A>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

How is Glanzmann thrombasthenia inherited?

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

ITGA2B p.Pro230=

c.690A>C · rs776840984 · VCV740616

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

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

PM2_Supporting BP7 BP4

Curation rationale (ClinGen, verbatim)

After a comprehensive literature search of the synonymous variant NM_000419.5(ITGA2B):c.690A>C (p.Pro230=), no individuals with Glanzmann thrombasthenia were reported with the variant. The variant has a minor allele frequency of 0.00002891 (1/34592 alleles) in the Latino population population in gnomAD, which meets the threshold criteria for PM2_supporting. In silico predictor spliceAI revealed that the synonymous mutation is not expected to impact splicing and a PhyloP score of -0.982 shows that the nucleotide position is not highly conserved (BP4, BP7). In summary, this variant is classified as likely benign for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD-VCEP: PM2_Supporting, BP4, BP7. (PD VCEP specifications version 2.1).

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 -0.47	GERP -2.7, phastCons 0.086
Overall
CADD	9.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,988 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00105% 17/1,613,728 alleles · ultra-rare exomes 14/1,461,842 · genomes 3/151,886 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,998
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.000763%	131,106

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.Pro230=
Coding: c.690A>C
MANE Select: NM_000419
dbSNP: rs776840984
Type: single nucleotide variant
Location: chr17:44385057 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 230: 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

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-pro230 (accessed [today's date]).

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