Is CEP104 p.Glu697fs (c.2088_2091del) pathogenic?

CEP104 p.Glu697fs (c.20882091del) is classified Likely pathogenic in CEP104 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-15). Very rare (popmax 0.000509%, nfe); Associated with intellectual developmental disorder, autosomal recessive 77.

What condition is associated with CEP104 p.Glu697fs (c.2088_2091del)?

CEP104 p.Glu697fs (c.2088_2091del) is associated with intellectual developmental disorder, autosomal recessive 77, Joubert syndrome 25 (ClinVar).

How common is CEP104 p.Glu697fs (c.2088_2091del) in the general population?

CEP104 p.Glu697fs (c.2088_2091del) is very rare (popmax 0.000509%, nfe) (gnomAD).

CEP104 p.Glu697fs

c.2088_2091del · VCV3583701

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

intellectual developmental disorder, autosomal recessive 77

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 15 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,177,674 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000414% 6/1,449,638 alleles · very 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: CEP104
Protein: p.Glu697fs
Coding: c.2088_2091del
MANE Select: NM_014704
Type: Microsatellite
Location: chr1:3829326 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB
Residue 697: a UniProt-annotated variant site (in mrt77)

Full CEP104 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder, autosomal recessive 77 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Joubert syndrome 25

Similar variants

CEP104 p.Leu100_Cys101insTer Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Ter926AlaextTer? Uncertain significance ★ same condition
CEP104 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Arg55Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Gln694fs Pathogenic ★★ same condition
CEP104 p.Glu627Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Glu762fs Likely pathogenic ★★ same condition
CEP104 p.Lys270Ter 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/cep104-p-glu697fs (accessed [today's date]).

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