ITGA2B p.Val286=
c.858C>T · rs376672078 · VCV323562
ClinGen expert panel — Platelet Disorders VCEP
Likely Benign for Glanzmann thrombasthenia. Applied ACMG criteria (verbatim):
PM2_Supporting BP7 BP4
Curation rationale (ClinGen, verbatim)
NM_000419.5(ITGA2B):c.858C>T (p.Val286=) is a rare synonymous variant. The highest population minor allele frequency in gnomAD v4.0 is 0.00005254 (64/1179956 alleles) in the European (non-Finnish) population, which is lower than the ClinGen PD VCEP threshold (<0.0001; PM2_Supporting). This variant has not been reported in any affected individuals in published literature but has been reported once in a healthy individual as part of a population screen. In silico splicing tools predict this synonymous variant to have no impact on splicing and this is not a highly conserved nucleotide (BP4, BP7). In summary, this variant meets criteria for PM2_supporting, BP4, and BP7; and is therefore classified as likely 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 | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3 | GERP -3 |
| Overall | ||
| CADD | 3.546 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
| European (non-Finnish)grpmax | 0.00525% | 19,032 |
Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Val286=
- Coding
- c.858C>T
- MANE Select
- NM_000419
- dbSNP
- rs376672078
- Type
- single nucleotide variant
- Location
- chr17:44384344 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.00 · 80 PDB
- Residue 286
- a β-strand
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
- ITGA2B p.Val286Asp Likely pathogenic ★★★ same residue
- ITGA2B p.Val286fs 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
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-val286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown