CRB1 p.Pro1400fs
c.4199del · VCV3751403
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
2
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 | escapes | premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -9 | GERP -3.7 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CRB1
- Protein
- p.Pro1400fs
- Coding
- c.4199del
- MANE Select
- NM_201253
- Type
- Deletion
- Location
- chr1:197477853 (GRCh38)
- Gene constraint
- LOEUF 0.776 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.19 · 1 PDB
- Residue 1400
- a UniProt-annotated variant site (in lca8); a UniProt-annotated variant site (found in a patient with early-onset retinal dystrophy; uncertain significance); an α-helix; the 'interaction with epb41l5' region
Disease context
Leber congenital amaurosis 8 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsAlso linked: retinitis pigmentosa 12
For Leber congenital amaurosis (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- 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
- CRB1 p.Cys1211fs 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-pro1400fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown