Is GP1BB p.Pro90Arg (c.269C>G) pathogenic?

GP1BB p.Pro90Arg (c.269C>G) is classified Likely pathogenic in GP1BB (ClinVar, Expert panel, 1 submitter; last evaluated 2025-02-18). AlphaMissense: ambiguous (0.4792); Absent from gnomAD v4.1; Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BB p.Pro90Arg (c.269C>G)?

GP1BB p.Pro90Arg (c.269C>G) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BB p.Pro90Arg (c.269C>G) in the general population?

GP1BB p.Pro90Arg (c.269C>G) is absent from gnomAD v4.1 (gnomAD).

How is Bernard-Soulier syndrome inherited?

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

What do computational predictors say about GP1BB p.Pro90Arg (c.269C>G)?

AlphaMissense predicts ambiguous (score 0.4792) — an in-silico prediction, not a clinical call.

GP1BB p.Pro90Arg

c.269C>G · VCV3775056

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4792 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
AlphaMissense	0.4792	ambiguous
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -10.39	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GP1BB
Protein: p.Pro90Arg
Coding: c.269C>G
MANE Select: NM_000407
Type: single nucleotide variant
Location: chr22:19724112 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB
Residue 90: the lrrct domain

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.Pro90Ser Likely pathogenic ★★★ same residue
GP1BB p.Pro90Leu Uncertain significance ★ ⚠ same residue
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

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-pro90arg (accessed [today's date]).

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