Is GP1BB p.Pro71Leu (c.212C>T) pathogenic?

GP1BB p.Pro71Leu (c.212C>T) is classified Uncertain significance in GP1BB (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). AlphaMissense: likely benign (0.3001); Very rare (popmax 8.81e-05%, nfe); Associated with thrombocytopenia.

What condition is associated with GP1BB p.Pro71Leu (c.212C>T)?

GP1BB p.Pro71Leu (c.212C>T) is associated with thrombocytopenia (ClinVar).

How common is GP1BB p.Pro71Leu (c.212C>T) in the general population?

GP1BB p.Pro71Leu (c.212C>T) is very rare (popmax 8.81e-05%, nfe) (gnomAD).

What do computational predictors say about GP1BB p.Pro71Leu (c.212C>T)?

AlphaMissense predicts likely benign (score 0.3001) — an in-silico prediction, not a clinical call.

GP1BB p.Pro71Leu

c.212C>T · rs1424014771 · VCV627272

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.81e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

thrombocytopenia

Computational evidence

Protein change
AlphaMissense	0.3001	likely benign
REVEL	0.616	indeterminate
SaProt	LLR -11.08	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.81e-05% European (non-Finnish) · 1/1,135,282 alleles

Overall 6.62e-05% 1/1,510,260 alleles · very rare exomes 1/1,358,170 · genomes 0/152,090 · joint denominator

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.Pro71Leu
Coding: c.212C>T
MANE Select: NM_000407
dbSNP: rs1424014771
Type: single nucleotide variant
Location: chr22:19724055 (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.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.Pro145Arg Uncertain significance ★ ⚠ same condition
GP1BB p.Pro71_Leu81del Uncertain significance ★ same residue
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-pro71leu (accessed [today's date]).

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