Is GP1BA p.Ser55fs (c.165_168del) pathogenic?

GP1BA p.Ser55fs (c.165168del) is classified Likely pathogenic in GP1BA (ClinVar, Expert panel, 2 submitters; last evaluated 2025-02-11). No gnomAD frequency available for this variant; Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BA p.Ser55fs (c.165_168del)?

GP1BA p.Ser55fs (c.165_168del) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BA p.Ser55fs (c.165_168del) in the general population?

GP1BA p.Ser55fs (c.165_168del) is no gnomAD frequency available for this variant (gnomAD).

How is Bernard-Soulier syndrome inherited?

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

GP1BA p.Ser55fs

c.165_168del · rs2151107696 · VCV2736403

Likely pathogenic Expert panel

Classification

Likely pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Bernard-Soulier syndrome

ClinGen expert panel — Platelet Disorders VCEP

Likely Pathogenic for Bernard-Soulier syndrome. Applied ACMG criteria (verbatim):

PVS1_Strong PM3_Supporting PM2_Supporting PS3_Supporting PP4

Curation rationale (ClinGen, verbatim)

The c.165_168del (p.Ser55ArgfsTer12) variant in GP1BA is a frameshift variant that may cause a premature stop codon that is predicted to escape nonsense mediated decay, however it is a truncation of a functionally important region (removes the final 598 amino acids) in a gene where loss-of-function is an established disease mechanism (PVS1_Strong). At least one patient (Patient 1 in PMID: 11054083) with this variant had aggregation absent for ristocetin and present for all other agonists, which is highly specific for Bernard-Soulier syndrome (PP4). They also had a history of recurrent epistaxis and spontaneous skin bruises and a low platelet count (84x10^9/l). This variant has been detected in at least 2 probands with Bernard-Soulier syndrome. One of those individuals was compound heterozygous for this variant and the c.1601_1602del (p.Tyr534CysfsTer?) variant in GP1BA, confirmed in trans by parental testing (PMID: 11054083). This second variant was classified as Pathogenic by the VCEP. (not included here to avoid circularity). The other proband was homozygous for the c.165_168del (p.Ser55ArgfsTer12) variant (PMID: 18791947; PM3_Supporting). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). From PMID: 11054083, flow cytometric analysis was performed for GP Iba on CHO cells transiently transfected with the WT + c.165_168del (p.Ser55ArgfsTer12), which had around 60% WT expression levels above sham. They also tested c.165_168del + c.1601_1602del, which had around 5% WT expression levels above sham. Due to the methods used in this assay (where c.165_168del was not tested independently), the usual threshold of <25% WT levels to apply PS3_supporting is not the appropriate measure. The 60% expression of WT + c.165_168del is considered sufficient, particularly in light of the c.165_168del + c.1601_1602del, which had around 5% WT expression levels (PS3_supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive Bernard-Soulier syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen PD VCEP: PVS1_Strong, PP4, PM2_Supporting and PM3_Supporting, PS3_Supporting (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.
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 0.093	GERP -2.1, phastCons 0.002

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GP1BA
Protein: p.Ser55fs
Coding: c.165_168del
MANE Select: NM_000173
dbSNP: rs2151107696
Type: Microsatellite
Location: chr17:4932765 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB

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

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GP1BA p.Asn32fs Likely pathogenic ★★★ same condition
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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-ser55fs (accessed [today's date]).

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