Is GP1BB p.Pro72Leu (c.215C>T) pathogenic?

GP1BB p.Pro72Leu (c.215C>T) is classified Uncertain significance in GP1BB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-13). AlphaMissense: likely benign (0.1076); Ultra-rare (popmax 0.059%, afr); Associated with Bernard-Soulier syndrome.

What condition is associated with GP1BB p.Pro72Leu (c.215C>T)?

GP1BB p.Pro72Leu (c.215C>T) is associated with Bernard-Soulier syndrome (ClinVar).

How common is GP1BB p.Pro72Leu (c.215C>T) in the general population?

GP1BB p.Pro72Leu (c.215C>T) is ultra-rare (popmax 0.059%, afr) (gnomAD).

How is Bernard-Soulier syndrome inherited?

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

What do computational predictors say about GP1BB p.Pro72Leu (c.215C>T)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

GP1BB p.Pro72Leu

c.215C>T · rs755380704 · VCV1034192

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.059%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Bernard-Soulier syndrome

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.172	moderately benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.32	GERP -2.7
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	16.24	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 0.059% African / African-American · 41/69,448 alleles

Filtering AF 0.0447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0396%

Overall 0.00351% 53/1,509,024 alleles · ultra-rare exomes 27/1,356,938 · genomes 26/152,086 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.059%	1,694
Admixed American	0.00822%	12,160
Remaining individualsnot grpmax-eligible	0.00171%	58,498
European (non-Finnish)	0.000617%	162,094

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.Pro72Leu
Coding: c.215C>T
MANE Select: NM_000407
dbSNP: rs755380704
Type: single nucleotide variant
Location: chr22:19724058 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI 0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.43 · 3 PDB
Residue 72: a turn

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.Asn89Asp Likely pathogenic ★★★ same condition
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GP1BB p.Cys147Ser Likely pathogenic ★★★ ⚠ same condition
GP1BB p.Cys30Tyr Likely pathogenic ★★★ same condition
GP1BB p.Cys32Ter Likely pathogenic ★★★ same condition
GP1BB p.Glu136Ter Likely pathogenic ★★★ same condition
GP1BB p.Leu16Pro 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-pro72leu (accessed [today's date]).

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