ITGA2B p.Pro71Arg
c.212C>G · rs2510085546 · VCV2506413
ClinGen expert panel — Platelet Disorders VCEP
Likely Pathogenic for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):
PM2_Supporting PP4_Strong PP3_supporting
Curation rationale (ClinGen, verbatim)
The NM_000419.5(ITGA2B):c.212C>G (p.Pro71Arg) missense variant has been reported in at least one Glanzmann thrombasthenia patient (PMID: 21113249). Patient GE displayed mucocutaneous bleeding and impaired aggregation with all agonists except ristocetin, which is highly specific for Glanzmann thrombasthenia . Additionally, αIIbβ3 surface expression was reduced to <1%, as measured by flow cytometry, and there was<1% binding to PAC-1. (PP4_strong). The full genotype of Patient GE was reported later in Pilgrimm-Thorp (2012) Haemophilia 18S3 157 and a PhD dissertation from D. Pillitteri, the patient is compound heterozygous for this variant and Leu684Arg (classified VUS by the PD VCEP; PM3_NotMet). The Pro71Arg variant is absent from gnomAD v4.1 (PM2_Supporting) and the computational predictor REVEL gives a score of 0.809, which is above the ClinGen PD VCEP threshold of >0.7 and predicts a damaging effect on function (PP3). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Glanzmann Thrombasthenia based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PP4_strong, PM2_supporitng, PP3_supporting.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7257 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.809 | moderately pathogenic-leaning |
| SaProt | LLR -14.14 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 4,459 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 29.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
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.Pro71Arg
- Coding
- c.212C>G
- MANE Select
- NM_000419
- dbSNP
- rs2510085546
- Type
- single nucleotide variant
- Location
- chr17:44386108 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.00 · 80 PDB
Disease context
Glanzmann thrombasthenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Glanzmann thrombasthenia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
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- 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-pro71arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown