Is CEP290 p.Val2445fs (c.7328_7332dup) pathogenic?

CEP290 p.Val2445fs (c.73287332dup) is classified Pathogenic in CEP290 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-05-01). Ultra-rare (popmax 0.0269%, eas); Associated with Inborn genetic diseases.

What condition is associated with CEP290 p.Val2445fs (c.7328_7332dup)?

CEP290 p.Val2445fs (c.7328_7332dup) is associated with Inborn genetic diseases, Joubert syndrome 5, Senior-Loken syndrome 6 (ClinVar).

How common is CEP290 p.Val2445fs (c.7328_7332dup) in the general population?

CEP290 p.Val2445fs (c.7328_7332dup) is ultra-rare (popmax 0.0269%, eas) (gnomAD).

CEP290 p.Val2445fs

c.7328_7332dup · rs747138345 · VCV663263

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0269%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3	GERP -3.1, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0269% East Asian · 12/44,682 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000826% 12/1,453,574 alleles · ultra-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.Val2445fs
Coding: c.7328_7332dup
MANE Select: NM_001009894 · reported on NM_025114
dbSNP: rs747138345
Type: Microsatellite
Location: chr12:88049291 (GRCh38)

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

Disease context

Inborn genetic diseases — 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 Joubert syndrome Meckel syndrome Leber congenital amaurosis nephronophthisis

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-val2445fs (accessed [today's date]).

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