Is CEP290 p.Ile232fs (c.694dup) pathogenic?

CEP290 p.Ile232fs (c.694dup) is classified Pathogenic in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-16). Absent from gnomAD; Associated with Joubert syndrome.

What condition is associated with CEP290 p.Ile232fs (c.694dup)?

CEP290 p.Ile232fs (c.694dup) is associated with Joubert syndrome, Meckel syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Ile232fs (c.694dup) in the general population?

CEP290 p.Ile232fs (c.694dup) is absent from gnomAD (gnomAD).

CEP290 p.Ile232fs

c.694dup · rs2501476639 · VCV2086546

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

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 10 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.2	GERP 2.4, 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: CEP290
Protein: p.Ile232fs
Coding: c.694dup
MANE Select: NM_025114
dbSNP: rs2501476639
Type: Duplication
Location: chr12:88129851 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 232: the 'self-association (with itself or c-terminus)' region; a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss)

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: Meckel syndrome nephronophthisis

Similar variants

CEP290 p.Asn85fs Likely pathogenic ★★★ same condition
CEP290 p.Asp450fs Likely pathogenic ★★★ same condition
CEP290 p.Lys1042Ter Pathogenic ★★★ same condition
CEP290 p.Phe2466fs Uncertain significance ★★★ same condition
CEP290 c.6818_6818+1dup Likely pathogenic ★★ same condition
CEP290 p.Arg1072fs Pathogenic/Likely pathogenic ★★ same condition
CEP290 p.Arg1084fs Pathogenic ★★ same condition
CEP290 p.Arg1237fs 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-ile232fs (accessed [today's date]).

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