Is CRB1 p.Pro89fs (c.266del) pathogenic?

CRB1 p.Pro89fs (c.266del) is classified Pathogenic in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-27). Very rare (popmax 8.47e-05%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with CRB1 p.Pro89fs (c.266del)?

CRB1 p.Pro89fs (c.266del) is associated with inherited retinal dystrophy (ClinVar).

How common is CRB1 p.Pro89fs (c.266del) in the general population?

CRB1 p.Pro89fs (c.266del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CRB1 p.Pro89fs

c.266del · VCV3381788

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.59	GERP -2.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,040 alleles

Overall 6.84e-05% 1/1,461,888 alleles · very rare

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: CRB1
Protein: p.Pro89fs
Coding: c.266del
MANE Select: NM_201253
Type: Deletion
Location: chr1:197328614 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 89: a disulfide bond; the egf-like 2 domain

Full CRB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRB1 c.652+3_652+6del Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Asn418fs Likely pathogenic ★ same condition
CRB1 p.Cys1321fs Likely pathogenic ★ same condition
CRB1 p.Glu1280fs Pathogenic ★ same condition
CRB1 p.Ser563fs Likely pathogenic ★ same condition
CRB1 p.Ile167_Gly169del Conflicting classifications of pathogenicity ★ same condition
CRB1 p.Pro89Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
CRB1 p.Ser635fs 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/crb1-p-pro89fs (accessed [today's date]).

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