Is GP9 p.Ter178= (c.533G>A) pathogenic?

GP9 p.Ter178= (c.533G>A) is classified Conflicting classifications of pathogenicity in GP9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-25). Rare (popmax 0.224%, eas); Associated with Bernard-Soulier syndrome.

What condition is associated with GP9 p.Ter178= (c.533G>A)?

GP9 p.Ter178= (c.533G>A) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP9 p.Ter178= (c.533G>A) in the general population?

GP9 p.Ter178= (c.533G>A) is rare (popmax 0.224%, eas) (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.Ter178=

c.533G>A · rs566144272 · VCV343223

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.224%, eas)

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP 0.021, phastCons 0.49
Overall
CADD	5.565	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

Grpmax group 0.224% East Asian · 92/41,116 alleles

Filtering AF 0.187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.173%

Overall 0.00621% 96/1,544,854 alleles · rare exomes 88/1,392,562 · genomes 8/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.224%	447
Remaining individualsnot grpmax-eligible	0.00502%	19,906
European (non-Finnish)	8.74e-05%	1,144,150

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.Ter178=
Coding: c.533G>A
MANE Select: NM_000174
dbSNP: rs566144272
Type: single nucleotide variant
Location: chr3:129062272 (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-ter178 (accessed [today's date]).

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