GP1BB p.Pro145Ser
c.433C>T · rs544345018 · VCV2581461
ClinGen expert panel — Platelet Disorders VCEP
Benign for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):
BP4 BA1
Curation rationale (ClinGen, verbatim)
The NM_000407.5(GP1BB):c.433C>T (p.Pro145Ser) variant in GP1BB is a missense variant that has a Grpmax Filtering allele frequency in gnomAD v4.1.1 of 0.002995 (based on 215/63908 alleles) in the African/African American population, which is higher than the ClinGen PD VCEP threshold (>0.001), and there for meets benign by frequency in the general population (BA1). The variant is predicted to not affect the protein (REVEL score of 0.115; BP4) In summary, this variant meets the criteria to be classified as benign for autosomal recessive Bernard-Soulier syndrome. ACMG/AMP criteria applied, as specified by the ClinGen Platelet Disorders VCEP (specifications version 1.1.0): BA1, BP4.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0805 | likely benign |
|---|---|---|
| REVEL | 0.115 | moderately benign-leaning |
| SaProt | LLR -6.05 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.47 | GERP -2.3 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic |
| Overall | ||
| CADD | 7.462 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.336% | 297 |
| Admixed American | 0.0431% | 2,318 |
| Remaining individualsnot grpmax-eligible | 0.017% | 5,899 |
| European (non-Finnish) | 0.000492% | 203,153 |
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
- GP1BB
- Protein
- p.Pro145Ser
- Coding
- c.433C>T
- MANE Select
- NM_000407
- dbSNP
- rs544345018
- Type
- single nucleotide variant
- Location
- chr22:19724276 (GRCh38)
- Gene constraint
- LOEUF 1.922 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 88.43 · 3 PDB
Similar variants
- GP1BB p.Pro145Arg Uncertain significance ★ ⚠ same residue
- GP1BB p.Asn89Asp Likely pathogenic ★★★ same type
- GP1BB p.Asn89Thr Likely pathogenic ★★★ same type
- GP1BB p.Cys141Ter Pathogenic ★★★ same type
- GP1BB p.Cys147Ser Likely pathogenic ★★★ ⚠ same type
- GP1BB p.Cys30Tyr Likely pathogenic ★★★ same type
- GP1BB p.Cys32Ter Likely pathogenic ★★★ same type
- GP1BB p.Glu136Ter Likely pathogenic ★★★ same type
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/gp1bb-p-pro145ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown