Is CRB1 p.Pro137fs (c.410del) pathogenic?

CRB1 p.Pro137fs (c.410del) is classified Pathogenic in CRB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-21). Absent from gnomAD; Associated with Leber congenital amaurosis 8.

What condition is associated with CRB1 p.Pro137fs (c.410del)?

CRB1 p.Pro137fs (c.410del) is associated with Leber congenital amaurosis 8 (ClinVar).

How common is CRB1 p.Pro137fs (c.410del) in the general population?

CRB1 p.Pro137fs (c.410del) is absent from gnomAD (gnomAD).

How is Leber congenital amaurosis inherited?

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

CRB1 p.Pro137fs

c.410del · rs1558057153 · VCV587386

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Leber congenital amaurosis 8

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 9.1	GERP 1.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRB1
Protein: p.Pro137fs
Coding: c.410del
MANE Select: NM_201253
dbSNP: rs1558057153
Type: Deletion
Location: chr1:197328759 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.19 · 1 PDB
Residue 137: a disulfide bond; the egf-like 3 domain

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

Disease context

Leber congenital amaurosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CRB1 p.Pro137= Uncertain significance ★ same residue
CRB1 c.652+3_652+6del Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Ala1374fs Pathogenic ★★ same condition
CRB1 p.Asn7fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Asp1299fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Asp47fs Pathogenic ★★ same condition
CRB1 p.Cys1143fs Pathogenic/Likely pathogenic ★★ same condition
CRB1 p.Cys1148fs Pathogenic/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/crb1-p-pro137fs (accessed [today's date]).

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