Is GP1BB p.Pro145Arg (c.434C>G) pathogenic?

GP1BB p.Pro145Arg (c.434C>G) is classified Uncertain significance in GP1BB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). AlphaMissense: likely benign (0.0718); Very rare (popmax 0.0033%, eas); Associated with thrombocytopenia.

What condition is associated with GP1BB p.Pro145Arg (c.434C>G)?

GP1BB p.Pro145Arg (c.434C>G) is associated with thrombocytopenia (ClinVar).

How common is GP1BB p.Pro145Arg (c.434C>G) in the general population?

GP1BB p.Pro145Arg (c.434C>G) is very rare (popmax 0.0033%, eas) (gnomAD).

What do computational predictors say about GP1BB p.Pro145Arg (c.434C>G)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

GP1BB p.Pro145Arg

c.434C>G · rs1051842719 · VCV627068

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

thrombocytopenia

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.209	benign-leaning
SaProt	LLR -4.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3	GERP -2.3
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	5.176	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0033% East Asian · 1/30,322 alleles

Filtering AF 0.00169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.00282% 36/1,274,772 alleles · very rare exomes 34/1,123,266 · genomes 2/151,506 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0191%	5,247
East Asiangrpmax	0.0033%	30,322
Finnishnot grpmax-eligible	0.00268%	37,294
European (non-Finnish)	0.00246%	40,635

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: GP1BB
Protein: p.Pro145Arg
Coding: c.434C>G
MANE Select: NM_000407
dbSNP: rs1051842719
Type: single nucleotide variant
Location: chr22:19724277 (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

thrombocytopenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GP1BB p.Pro145Ser Uncertain significance ★ ⚠ same residue
GP1BB p.Leu16Pro Likely pathogenic ★★★ ⚠ same condition
GP1BB p.Ser48Ter Likely pathogenic ★★★ same condition
GP1BB p.Trp46Ter Likely pathogenic ★★★ same condition
GP1BB p.Leu132Gln Likely pathogenic ★★ same condition
GP1BB p.Glu136Gly Uncertain significance ★ ⚠ same condition
GP1BB p.Pro71Leu Uncertain significance ★ ⚠ same condition
GP1BB p.Pro79_Leu81del 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-pro145arg (accessed [today's date]).

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