Is CEP290 p.Phe1435fs (c.4305del) pathogenic?

CEP290 p.Phe1435fs (c.4305del) is classified Likely pathogenic in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). Associated with Autosomal recessive CEP290-related disorders.

What condition is associated with CEP290 p.Phe1435fs (c.4305del)?

CEP290 p.Phe1435fs (c.4305del) is associated with Autosomal recessive CEP290-related disorders (ClinVar).

CEP290 p.Phe1435fs

c.4305del · VCV4850192

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Autosomal recessive CEP290-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	predicted	premature termination codon in exon 34 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1

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

Variant & gene context

Gene: CEP290
Protein: p.Phe1435fs
Coding: c.4305del
MANE Select: NM_025114
Type: Deletion
Location: chr12:88086171 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 1435: 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)

Full CEP290 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Autosomal recessive CEP290-related disorders

Similar variants

CEP290 c.2052+1_2052+2del Pathogenic ★★ same condition
CEP290 p.Lys1058_Ile1059insTer Pathogenic ★★ same condition
CEP290 p.Phe1435= Likely benign ★ same residue
CEP290 p.Phe1435Leu Uncertain significance ⚠ same residue
CEP290 c.1623+1G>A Pathogenic ★★ same condition
CEP290 p.Leu1884fs Pathogenic ★★ same condition
CEP290 p.Gln852fs Pathogenic ★ same condition
CEP290 c.4438-3del Pathogenic ★★★ same type

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-phe1435fs (accessed [today's date]).

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