Is CEP83 p.Glu669fs (c.2007del) pathogenic?

CEP83 p.Glu669fs (c.2007del) is classified Pathogenic in CEP83 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-07). Ultra-rare (popmax 0.015%, amr); Associated with nephronophthisis 18.

What condition is associated with CEP83 p.Glu669fs (c.2007del)?

CEP83 p.Glu669fs (c.2007del) is associated with nephronophthisis 18 (ClinVar).

How common is CEP83 p.Glu669fs (c.2007del) in the general population?

CEP83 p.Glu669fs (c.2007del) is ultra-rare (popmax 0.015%, amr) (gnomAD).

How is Nephronophthisis inherited?

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

CEP83 p.Glu669fs

c.2007del · rs922686745 · VCV1070747

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Conditions

nephronophthisis 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (17 of 17) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 2.3, phastCons 1
Overall
CADD	28.1	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 0.015% Admixed American · 9/59,914 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.000872% 14/1,606,224 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,657
Remaining individualsnot grpmax-eligible	0.00482%	20,726
African / African-American	0.00268%	37,347

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: CEP83
Protein: p.Glu669fs
Coding: c.2007del
MANE Select: NM_016122
dbSNP: rs922686745
Type: Deletion
Location: chr12:94308912 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.90

Full CEP83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

nephronophthisis 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephronophthisis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Finland)

Similar variants

CEP83 p.Ala556fs Likely pathogenic ★ same condition
CEP83 p.Arg514fs Pathogenic ★ same condition
CEP83 p.Asp354fs Pathogenic ★ same condition
CEP83 p.Glu437fs Pathogenic ★ same condition
CEP83 p.Leu203fs Pathogenic ★ same condition
CEP83 p.Lys390fs Pathogenic ★ same condition
CEP83 p.Lys412fs Pathogenic ★ same condition
CEP83 p.Met105fs 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/cep83-p-glu669fs (accessed [today's date]).

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