Is GP1BB p.Leu97Phe (c.289C>T) pathogenic?

GP1BB p.Leu97Phe (c.289C>T) is classified Uncertain significance in GP1BB (ClinVar, Expert panel, 1 submitter; last evaluated 2026-04-02). AlphaMissense: likely pathogenic (0.7235); No allele count reported in gnomAD v4.1 (AN 1,388,614); Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BB p.Leu97Phe (c.289C>T)?

GP1BB p.Leu97Phe (c.289C>T) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BB p.Leu97Phe (c.289C>T) in the general population?

GP1BB p.Leu97Phe (c.289C>T) is no allele count reported in gnomAD v4.1 (AN 1,388,614) (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.Leu97Phe (c.289C>T)?

AlphaMissense predicts likely pathogenic (score 0.7235) — an in-silico prediction, not a clinical call.

GP1BB p.Leu97Phe

c.289C>T · VCV4849249

Uncertain significance Expert panel

Classification

Uncertain significance

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7235 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,388,614)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
AlphaMissense	0.7235	likely pathogenic
REVEL	0.535	indeterminate
SaProt	LLR -11.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.4	GERP -1.9
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,388,614). 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: GP1BB
Protein: p.Leu97Phe
Coding: c.289C>T
MANE Select: NM_000407
Type: single nucleotide variant
Location: chr22:19724132 (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 97: an α-helix; 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

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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-leu97phe (accessed [today's date]).

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