Is GP9 p.Pro146= (c.438G>A) pathogenic?

GP9 p.Pro146= (c.438G>A) is classified Conflicting classifications of pathogenicity in GP9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-09). Ultra-rare (popmax 0.0275%, sas); Associated with Bernard-Soulier syndrome.

What condition is associated with GP9 p.Pro146= (c.438G>A)?

GP9 p.Pro146= (c.438G>A) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP9 p.Pro146= (c.438G>A) in the general population?

GP9 p.Pro146= (c.438G>A) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

How is Bernard-Soulier syndrome inherited?

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

GP9 p.Pro146=

c.438G>A · rs767278544 · VCV343221

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6	GERP -2.5
Overall
CADD	0.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% South Asian · 24/87,426 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00292% 46/1,575,630 alleles · ultra-rare exomes 39/1,423,402 · genomes 7/152,228 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,643
African / African-American	0.00404%	24,761
Remaining individualsnot grpmax-eligible	0.00327%	30,542
European (non-Finnish)	0.00146%	68,542

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GP9
Protein: p.Pro146=
Coding: c.438G>A
MANE Select: NM_000174
dbSNP: rs767278544
Type: single nucleotide variant
Location: chr3:129062177 (GRCh38)
Structure: AlphaFold pLDDT 84.43 · 2 PDB

Full GP9 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

GP9 p.Asn61Ser Pathogenic ★★★ same condition
GP9 p.Cys135Tyr Likely pathogenic ★★★ ⚠ same condition
GP9 p.Cys24Arg Likely pathogenic ★★★ same condition
GP9 p.Cys38Arg Likely pathogenic ★★★ same condition
GP9 p.Cys89Tyr Pathogenic ★★★ same condition
GP9 p.Leu56Pro Likely pathogenic ★★★ same condition
GP9 p.Leu7Pro Likely pathogenic ★★★ ⚠ same condition
GP9 p.Phe71Cys 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/gp9-p-pro146 (accessed [today's date]).

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