ITGA2B p.Val982=
c.2946G>A · rs148263909 · VCV1803209
ClinGen expert panel — Platelet Disorders VCEP
Likely Benign for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):
BP7 BP4
Curation rationale (ClinGen, verbatim)
The c.2946G>A (p.Val982=) variant is a synonymous variant that is not predicted by SpliceAI to impact splicing and the nucleotide is only moderately conserved, as shown by phyloP score of 0.703 (BP4, BP7). The highest population minor allele frequency in gnomAD v3.1.2 is 0.0001448 (6/41436 alleles) in the African/African American population. This intermediate allele frequency is lower than the ClinGen PD VCEP threshold (>0.00158) for BS1 but higher than the threshold (<0.0001) for PM2_Supporting, so no allele frequency criteria were met. In addition, no cases of the variant segregating with Glanzmann thrombasthenia were found in the literature. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive Glanzmann Thrombasthenia with the following ACMG/AMP applied, as specified by the ClinGen PD VCEP: BP4, BP7 (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 0.15 | GERP -1.3, phastCons 0.007 |
| Overall | ||
| CADD | 5.695 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0267% | 3,752 |
| Middle Eastern | 0.0165% | 6,060 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| Admixed American | 0.005% | 20,009 |
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.Val982=
- Coding
- c.2946G>A
- MANE Select
- NM_000419
- dbSNP
- rs148263909
- Type
- single nucleotide variant
- Location
- chr17:44374468 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.00 · 80 PDB
- Residue 982
- a β-strand; a UniProt-annotated variant site (in gt1; much reduced surface expression of alpha-iib/beta-3 and a block in the maturation of pro-alpha-iib)
Disease context
Glanzmann thrombasthenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Glanzmann thrombasthenia 1
For Glanzmann thrombasthenia (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- ITGA2B p.Val982Met 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-val982 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown