ClinGen expert panel — Platelet Disorders VCEP
Benign for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):
BP7 BP4 BA1
Curation rationale (ClinGen, verbatim)
The synonymous variant NM_000173.7(GP1BA):c.1074A>G (p.Arg358=) is not predicted by SpliceAI to impact splicing (score 0.00; BP4). In addition, it occurs at a nucleotide that is not highly conserved as shown by phyloP score of 0.134386 (BP7). The Grpmax Filtering allele frequency in gnomAD v4.1 is 0.2116 (based on 9653/44866 alleles, including 1018 homozygotes) in the East Asian population, which is higher than the ClinGen PD VCEP threshold (>0.001; BA1). 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, BP7 (ClinGen Platelet Disorders 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 0.47 | GERP -0.12 |
| Overall | ||
| CADD | 1.897 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 21.5% | 5 |
| Admixed American | 13.2% | 8 |
| South Asian | 9.26% | 11 |
| Middle Eastern | 7.29% | 14 |
| Remaining individualsnot grpmax-eligible | 5.57% | 18 |
| Ashkenazi Jewishnot grpmax-eligible | 5.56% | 18 |
| European (non-Finnish) | 3.24% | 31 |
| African / African-American | 2.67% | 37 |
| Finnishnot grpmax-eligible | 2.62% | 38 |
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
- GP1BA
- Protein
- p.Arg358=
- Coding
- c.1074A>G
- MANE Select
- NM_000173
- dbSNP
- rs6067
- Type
- single nucleotide variant
- Location
- chr17:4933678 (GRCh38)
- Gene constraint
- LOEUF 1.289 · pLI 0.10 (gnomAD)
- Structure
- AlphaFold pLDDT 64.65 · 22 PDB
- Residue 358
- the 'disordered' region
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
- GP1BA p.Arg358_Trp359insTer Likely pathogenic ★★★ same residue
- GP1BA p.Cys225Arg Likely pathogenic ★★★ same condition
- GP1BA p.Cys81Arg Pathogenic ★★★ same condition
- GP1BA p.Gln346Ter Likely pathogenic ★★★ same condition
- GP1BA p.Glu347Ter Likely pathogenic ★★★ same condition
- GP1BA p.Leu145Pro Likely pathogenic ★★★ same condition
- GP1BA p.Ser267Ter Likely pathogenic ★★★ same condition
- GP1BA p.Ser486Ter 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/gp1ba-p-arg358 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown