GP9 p.Ala6=
c.18C>T · rs200376043 · VCV902701
ClinGen expert panel — Platelet Disorders VCEP
Benign for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
The c.18C>T (p.Ala6=) variant in GP9 is a synonymous variant that is not predicted by SpliceAI to impact splicing (score <0.1). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of -0.7486 (BP7 and BP4). The Grpmax Filtering allele frequency in gnomAD v4.1.0 is 0.001318 (based on 68/44866 alleles) in the South Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001), and therefore meets this criterion (BA1). This variant was observed by Illumina as part of a predisposition screen in an ostensibly healthy population, however, no cases of the variant segregating in Bernard Soulier Syndrome have been found in the literature. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: BA1, BP4 and BP7 (VCEP specifications version 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 -0.94 | GERP -4.7 |
| Overall | ||
| CADD | 4.569 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.152% | 660 |
| African / African-American | 0.00533% | 18,760 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,809 |
| Admixed American | 0.00333% | 29,990 |
| European (non-Finnish) | 0.000339% | 294,937 |
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
- GP9
- Protein
- p.Ala6=
- Coding
- c.18C>T
- MANE Select
- NM_000174
- dbSNP
- rs200376043
- Type
- single nucleotide variant
- Location
- chr3:129061757 (GRCh38)
- Structure
- AlphaFold pLDDT 84.43 · 2 PDB
Disease context
Bernard-Soulier syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Bernard-Soulier syndrome (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
Similar variants
- GP9 p.Asn61Ser Pathogenic ★★★ same condition
- GP9 p.Cys135Tyr Likely pathogenic ★★★ ⚠ same condition
- GP9 p.Cys24Arg Likely pathogenic ★★★ same condition
- GP9 p.Cys38Arg Likely pathogenic ★★★ same condition
- GP9 p.Cys89Tyr Pathogenic ★★★ same condition
- GP9 p.Leu56Pro Likely pathogenic ★★★ same condition
- GP9 p.Leu7Pro Likely pathogenic ★★★ ⚠ same condition
- GP9 p.Phe71Cys 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/gp9-p-ala6 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown