Is CEP290 p.Ser895fs (c.2682dup) pathogenic?

CEP290 p.Ser895fs (c.2682dup) is classified Pathogenic/Likely pathogenic in CEP290 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-01-09). Absent from gnomAD; Associated with retinitis pigmentosa.

What condition is associated with CEP290 p.Ser895fs (c.2682dup)?

CEP290 p.Ser895fs (c.2682dup) is associated with retinitis pigmentosa (ClinVar).

How common is CEP290 p.Ser895fs (c.2682dup) in the general population?

CEP290 p.Ser895fs (c.2682dup) is absent from gnomAD (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CEP290 p.Ser895fs

c.2682dup · rs1555216730 · VCV546718

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinitis pigmentosa

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 25 of 54
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.8, 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.Ser895fs
Coding: c.2682dup
MANE Select: NM_025114
dbSNP: rs1555216730
Type: Duplication
Location: chr12:88106809 (GRCh38)
Gene constraint: LOEUF 1.094 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 60.90
Residue 895: a UniProt-annotated variant site (in lca10; also found in a patient with night blindness and hearing loss); the 'interaction with iqcb1' region

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

Disease context

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

CEP290 p.Leu1155fs Likely pathogenic ★★★ same condition
CEP290 p.Leu1884fs Pathogenic ★★ same condition
CEP290 p.Ser895Pro Uncertain significance ★★ ⚠ same residue
CEP290 p.Ser895Ter Likely pathogenic ★ same residue
CEP290 c.2991+1655A>G Pathogenic ★★★ same condition
CEP290 p.Arg1926Pro Pathogenic ★★★ same condition
CEP290 p.Gln662Ter Pathogenic ★★★ same condition
CEP290 p.Lys75Glu 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-ser895fs (accessed [today's date]).

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