Is GP1BA p.Pro357fs (c.1064dup) pathogenic?

GP1BA p.Pro357fs (c.1064dup) is classified Likely pathogenic in GP1BA (ClinVar, Expert panel, 1 submitter; last evaluated 2025-03-06). Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BA p.Pro357fs (c.1064dup)?

GP1BA p.Pro357fs (c.1064dup) is associated with Bernard-Soulier syndrome (ClinVar).

How is Bernard-Soulier syndrome inherited?

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

GP1BA p.Pro357fs

c.1064dup · VCV3775063

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.38	GERP 0.17

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: GP1BA
Protein: p.Pro357fs
Coding: c.1064dup
MANE Select: NM_000173
Type: Duplication
Location: chr17:4933666 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB
Residue 357: the 'disordered' region

Full GP1BA 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

GP1BA p.Asn362fs Likely pathogenic ★★★ same condition
GP1BA p.Asp79fs Likely pathogenic ★★★ same condition
GP1BA p.Asp89fs Likely pathogenic ★★★ same condition
GP1BA p.Leu479fs Likely pathogenic ★★★ same condition
GP1BA p.Leu52fs Likely pathogenic ★★★ same condition
GP1BA p.Met338fs Likely pathogenic ★★★ same condition
GP1BA p.Ser420fs Likely pathogenic ★★★ same condition
GP1BA p.Ser486fs 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-pro357fs (accessed [today's date]).

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