CEP104 p.Ala686=
c.2058G>A · VCV4722620
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00268%, afr)
Conditions
1
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 -4.5 | GERP -3.5 |
| Overall | ||
| CADD | 4.181 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00268%
African / African-American · 2/74,590 alleles
Filtering AF
0.000445%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000167%
Overall
0.000621%
10/1,609,734 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00268% | 37,295 |
| South Asian | 0.00222% | 44,983 |
| European (non-Finnish) | 0.000509% | 196,526 |
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.Ala686=
- Coding
- c.2058G>A
- MANE Select
- NM_014704
- Type
- single nucleotide variant
- Location
- chr1:3829359 (GRCh38)
- Gene constraint
- LOEUF 0.851 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.75 · 2 PDB
- Residue 686
- a UniProt-annotated variant site (in mrt77); a UniProt-annotated variant site (in)
Similar variants
- CEP104 p.Ala686Val Benign ★★ ⚠ 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-ala686 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown