Is CEP104 p.Val8= (c.24A>G) pathogenic?

CEP104 p.Val8= (c.24A>G) is classified Likely benign in CEP104 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-06). Ultra-rare (popmax 0.0333%, afr); Associated with Joubert syndrome 25.

What condition is associated with CEP104 p.Val8= (c.24A>G)?

CEP104 p.Val8= (c.24A>G) is associated with Joubert syndrome 25 (ClinVar).

How common is CEP104 p.Val8= (c.24A>G) in the general population?

CEP104 p.Val8= (c.24A>G) is ultra-rare (popmax 0.0333%, afr) (gnomAD).

CEP104 p.Val8=

c.24A>G · VCV3655300

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0333%, afr)

Conditions

Joubert syndrome 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.2	GERP -3.7
Overall
CADD	0.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0333% African / African-American · 25/75,046 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00167% 27/1,614,052 alleles · ultra-rare exomes 11/1,461,722 · genomes 16/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0333%	3,002
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Val8=
Coding: c.24A>G
MANE Select: NM_014704
Type: single nucleotide variant
Location: chr1:3852384 (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.Val8Leu Uncertain significance ★ ⚠ same residue
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

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-val8 (accessed [today's date]).

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