CEP290 p.Arg1785fs
c.5352_5353dup · VCV4816222
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Leber congenital amaurosis
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 39 of 54 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.15 | GERP -1.4, phastCons 0.97 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CEP290
- Protein
- p.Arg1785fs
- Coding
- c.5352_5353dup
- MANE Select
- NM_025114
- Type
- Duplication
- Location
- chr12:88079102 (GRCh38)
- Gene constraint
- LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 60.90
- Residue 1785
- a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss); a UniProt-annotated variant site (in lca10); a UniProt-annotated variant site (in lca10, slsn6 and mks4); a UniProt-annotated variant site (in lca10 and slsn6)
Disease context
Leber congenital amaurosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Leber congenital amaurosis (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- CEP290 p.Asn1775fs Pathogenic ★★★ same condition
- CEP290 p.Lys1042Ter Pathogenic ★★★ same condition
- CEP290 c.6818_6818+1dup Likely pathogenic ★★ same condition
- CEP290 p.Arg1072fs Pathogenic/Likely pathogenic ★★ same condition
- CEP290 p.Arg1237fs Pathogenic/Likely pathogenic ★★ same condition
- CEP290 p.Arg1838fs Pathogenic/Likely pathogenic ★★ same condition
- CEP290 p.Asn2290fs Pathogenic ★★ same condition
- CEP290 p.Asn2430fs 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/cep290-p-arg1785fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown