GP1BA p.Phe208fs
c.624del · VCV3582323
ClinGen expert panel — Platelet Disorders VCEP
Likely Pathogenic for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):
PVS1_Strong PM3_Supporting PM2_Supporting PP4
Curation rationale (ClinGen, verbatim)
The c.624del (p.Phe208LeufsTer48) variant in GP1BA is a nonsense variant that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove >10% of the protein (PVS1_Strong). At least one patient (Patient BSS-2 in PMID:23300803) with this variant had aggregation absent for ristocetin and present for all other agonists as well as less than 10% expression of GPIba measured by flow cytometry, which is highly specific for Bernard-Soulier syndrome Additionally, the patient had macrothrombocytopenia which is consistent with Bernard-Soulier syndrome (PP4). This individual was homozygous for the variant (0.5 PM3 points, PM3_Supporting). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_Strong, PP4, PM3_Supporting and PM2_Supporting (VCEP specifications version 1.1).
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. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.12 | GERP -3.1, phastCons 0.2 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GP1BA
- Protein
- p.Phe208fs
- Coding
- c.624del
- MANE Select
- NM_000173
- Type
- Deletion
- Location
- chr17:4933223 (GRCh38)
- Gene constraint
- LOEUF 1.289 · pLI 0.10 (gnomAD)
- Structure
- AlphaFold pLDDT 64.65 · 22 PDB
- Residue 208
- a turn
Disease context
Bernard-Soulier syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: Bernard-Soulier syndrome, type A2, autosomal dominantplatelet-type von Willebrand diseasenonarteritic anterior ischemic optic neuropathy, susceptibility to
For Bernard-Soulier syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
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- GP1BA p.Leu531fs Likely pathogenic ★★★ same condition
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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/gp1ba-p-phe208fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown