Is GP1BB p.Pro195Arg (c.584C>G) pathogenic?

GP1BB p.Pro195Arg (c.584C>G) is classified Uncertain significance in GP1BB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.0945); Very rare (popmax 0.00413%, afr).

How common is GP1BB p.Pro195Arg (c.584C>G) in the general population?

GP1BB p.Pro195Arg (c.584C>G) is very rare (popmax 0.00413%, afr) (gnomAD).

What do computational predictors say about GP1BB p.Pro195Arg (c.584C>G)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

GP1BB p.Pro195Arg

c.584C>G · rs1936125083 · VCV2543666

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00413%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.461	indeterminate
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.65	GERP -0.018, phastCons 0.01
Regional constraint	o/e 1.03	unconstrained · MANE · 891 bp · p 0.61 · regional, not allelic
Overall
CADD	11.81	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 0.00413% African / African-American · 3/72,640 alleles

Filtering AF 0.0011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000504%

Overall 0.000259% 4/1,544,328 alleles · very rare exomes 3/1,392,158 · genomes 1/152,170 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00413%	24,213
European (non-Finnish)	8.74e-05%	1,144,516

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.Pro195Arg
Coding: c.584C>G
MANE Select: NM_000407
dbSNP: rs1936125083
Type: single nucleotide variant
Location: chr22:19724427 (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

Similar variants

GP1BB p.Asn89Asp Likely pathogenic ★★★ same type
GP1BB p.Asn89Thr Likely pathogenic ★★★ same type
GP1BB p.Cys141Ter Pathogenic ★★★ same type
GP1BB p.Cys147Ser Likely pathogenic ★★★ ⚠ same type
GP1BB p.Cys30Tyr Likely pathogenic ★★★ same type
GP1BB p.Cys32Ter Likely pathogenic ★★★ same type
GP1BB p.Glu136Ter Likely pathogenic ★★★ same type
GP1BB p.Leu16Pro Likely pathogenic ★★★ ⚠ same type

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-pro195arg (accessed [today's date]).

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