Is GP1BB p.Met1Val (c.1A>G) pathogenic?

GP1BB p.Met1Val (c.1A>G) is classified Pathogenic in GP1BB (ClinVar, Single submitter, 2 submitters; last evaluated 2019-02-21). Absent from gnomAD v4.1; Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BB p.Met1Val (c.1A>G)?

GP1BB p.Met1Val (c.1A>G) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BB p.Met1Val (c.1A>G) in the general population?

GP1BB p.Met1Val (c.1A>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.

GP1BB p.Met1Val

c.1A>G · rs1389191920 · VCV1338488

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.431	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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

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.Met1Val
Coding: c.1A>G
MANE Select: NM_000407
dbSNP: rs1389191920
Type: single nucleotide variant
Location: chr22:19723570 (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.Met1Leu Likely pathogenic ★★★ same residue
GP1BB p.Met1Thr Likely pathogenic ★ same residue
GP1BB p.Met1Ile Likely pathogenic 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

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-met1val (accessed [today's date]).

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