Is GP1BB p.Pro122fs (c.365del) pathogenic?

GP1BB p.Pro122fs (c.365del) is classified Likely pathogenic in GP1BB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-15). Very rare (popmax 0.000101%, nfe); Associated with GP1BB-related disorders.

What condition is associated with GP1BB p.Pro122fs (c.365del)?

GP1BB p.Pro122fs (c.365del) is associated with GP1BB-related disorders (ClinVar).

How common is GP1BB p.Pro122fs (c.365del) in the general population?

GP1BB p.Pro122fs (c.365del) is very rare (popmax 0.000101%, nfe) (gnomAD).

GP1BB p.Pro122fs

c.365del · VCV4946937

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000101%, nfe)

Conditions

GP1BB-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.36	GERP -2.4, phastCons 0.11

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000101% European (non-Finnish) · 1/986,530 alleles

Overall 0.000245% 3/1,224,346 alleles · very rare exomes 3/1,073,648 · genomes 0/150,698 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00613%	16,302
Finnishnot grpmax-eligible	0.00321%	31,142
European (non-Finnish)grpmax	0.000101%	986,534

Ashkenazi Jewish 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.Pro122fs
Coding: c.365del
MANE Select: NM_000407
Type: Deletion
Location: chr22:19724204 (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 122: a turn; the lrrct domain

Full GP1BB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GP1BB-related disorders

Similar variants

GP1BB p.Pro71_Leu81del Uncertain significance ★ same condition
GP1BB p.Ala152_Leu157del Uncertain significance same condition
GP1BB p.Ala150fs Pathogenic/Likely pathogenic ★★ same condition
GP1BB p.Leu146Phe Uncertain significance ★★ ⚠ same condition
GP1BB p.Cys32Arg Uncertain significance ★ ⚠ same condition
GP1BB p.Asp204Glu Uncertain significance ⚠ same condition
GP1BB p.Gly149Arg Uncertain significance same condition
GP1BB p.Ala8= Likely benign 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-pro122fs (accessed [today's date]).

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