Is GP1BB p.Pro5= (c.15G>A) pathogenic?

GP1BB p.Pro5= (c.15G>A) is classified Likely benign in GP1BB (ClinVar, Expert panel, 1 submitter; last evaluated 2025-02-11). Very rare (popmax 0.00035%, nfe); Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BB p.Pro5= (c.15G>A)?

GP1BB p.Pro5= (c.15G>A) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BB p.Pro5= (c.15G>A) in the general population?

GP1BB p.Pro5= (c.15G>A) is very rare (popmax 0.00035%, nfe) (gnomAD).

How is Bernard-Soulier syndrome inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GP1BB p.Pro5=

c.15G>A · VCV3775053

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00035%, nfe)

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.9	GERP -2.4, phastCons 0.99
Overall
CADD	13.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00035% European (non-Finnish) · 4/1,142,086 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000263% 4/1,523,452 alleles · very rare exomes 4/1,371,164 · genomes 0/152,288 · joint denominator

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.Pro5=
Coding: c.15G>A
MANE Select: NM_000407
Type: single nucleotide variant
Location: chr22:19723858 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB

Full GP1BB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bernard-Soulier syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bernard-Soulier syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages

Similar variants

GP1BB p.Asn89Asp Likely pathogenic ★★★ same condition
GP1BB p.Asn89Thr Likely pathogenic ★★★ same condition
GP1BB p.Cys141Ter Pathogenic ★★★ same condition
GP1BB p.Cys147Ser Likely pathogenic ★★★ ⚠ same condition
GP1BB p.Cys30Tyr Likely pathogenic ★★★ same condition
GP1BB p.Cys32Ter Likely pathogenic ★★★ same condition
GP1BB p.Glu136Ter Likely pathogenic ★★★ same condition
GP1BB p.Leu16Pro 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/gp1bb-p-pro5 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown