Is CEP104 p.Arg53Ter (c.157A>T) pathogenic?

CEP104 p.Arg53Ter (c.157A>T) is classified Pathogenic in CEP104 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Very rare (popmax 0.00449%, nfe); Associated with Joubert syndrome 25.

What condition is associated with CEP104 p.Arg53Ter (c.157A>T)?

CEP104 p.Arg53Ter (c.157A>T) is associated with Joubert syndrome 25 (ClinVar).

How common is CEP104 p.Arg53Ter (c.157A>T) in the general population?

CEP104 p.Arg53Ter (c.157A>T) is very rare (popmax 0.00449%, nfe) (gnomAD).

CEP104 p.Arg53Ter

c.157A>T · VCV3646990

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Conditions

Joubert syndrome 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 22
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP -1.6, phastCons 0.044
Overall
CADD	36.0	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 0.00449% European (non-Finnish) · 53/1,179,400 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00329% 53/1,611,298 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.Arg53Ter
Coding: c.157A>T
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3848738 (GRCh38)
Gene constraint: LOEUF 0.851 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.75 · 2 PDB

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

Disease context

Joubert syndrome 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP104 p.Arg299Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Arg55Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Glu627Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Lys270Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 p.Tyr253Ter Pathogenic/Likely pathogenic ★★ same condition
CEP104 c.1120-5T>A Uncertain significance ★★ same condition
CEP104 p.Ala269Thr Uncertain significance ★★ ⚠ same condition
CEP104 p.Ala28Val Uncertain significance ★★ ⚠ 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-arg53ter (accessed [today's date]).

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