Is CEP290 p.Phe1095fs (c.3285del) pathogenic?

CEP290 p.Phe1095fs (c.3285del) is classified Pathogenic/Likely pathogenic in CEP290 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-11-18). Very rare (popmax 0.00134%, afr); Associated with Joubert syndrome.

What condition is associated with CEP290 p.Phe1095fs (c.3285del)?

CEP290 p.Phe1095fs (c.3285del) is associated with Joubert syndrome, Joubert syndrome 5, Senior-Loken syndrome 6 (ClinVar).

How common is CEP290 p.Phe1095fs (c.3285del) in the general population?

CEP290 p.Phe1095fs (c.3285del) is very rare (popmax 0.00134%, afr) (gnomAD).

CEP290 p.Phe1095fs

c.3285del · rs1017496924 · VCV1405608

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

Joubert syndrome

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 28 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,854 alleles

Overall 0.000658% 1/152,060 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: CEP290
Protein: p.Phe1095fs
Coding: c.3285del
MANE Select: NM_025114
dbSNP: rs1017496924
Type: Deletion
Location: chr12:88093794 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 1095: 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

Joubert syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 5 Senior-Loken syndrome 6 Meckel syndrome, type 4 Leber congenital amaurosis 10 Bardet-Biedl syndrome 14 Meckel syndrome nephronophthisis

Similar variants

CEP290 c.4438-3del Pathogenic ★★★ same condition
CEP290 p.Asn737_Leu738insTer Pathogenic ★★★ same condition
CEP290 p.Ile556fs Pathogenic ★★★ same condition
CEP290 p.Lys1343fs Pathogenic ★★★ same condition
CEP290 p.Lys484fs Pathogenic ★★★ same condition
CEP290 p.Phe1950fs Pathogenic ★★★ same condition
CEP290 p.Ser319fs Pathogenic ★★★ same condition
CEP290 p.Thr55fs 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-phe1095fs (accessed [today's date]).

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