Is CEP290 p.Arg447fs (c.1338del) pathogenic?

CEP290 p.Arg447fs (c.1338del) is classified Pathogenic in CEP290 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-05-02). Absent from gnomAD; Associated with Meckel syndrome.

What condition is associated with CEP290 p.Arg447fs (c.1338del)?

CEP290 p.Arg447fs (c.1338del) is associated with Meckel syndrome, Joubert syndrome, nephronophthisis (ClinVar).

How common is CEP290 p.Arg447fs (c.1338del) in the general population?

CEP290 p.Arg447fs (c.1338del) is absent from gnomAD (gnomAD).

CEP290 p.Arg447fs

c.1338del · rs2039364798 · VCV945769

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

Meckel 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 14 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP -0.54, 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.Arg447fs
Coding: c.1338del
MANE Select: NM_025114
dbSNP: rs2039364798
Type: Deletion
Location: chr12:88121018 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 447: 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

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

Also linked: Joubert 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-arg447fs (accessed [today's date]).

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