CEP104 p.Pro838=
c.2514G>A · rs578262183 · VCV1615157
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0593%, sas)
Conditions
1
Joubert syndrome 25
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.082 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -8.3 | GERP -4 |
| Overall | ||
| CADD | 5.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0593%
South Asian · 54/91,090 alleles
Filtering AF
0.0466%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0421%
Overall
0.00781%
126/1,614,030 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0593% | 1,687 |
| Middle Eastern | 0.0493% | 2,027 |
| Admixed American | 0.0283% | 3,530 |
| East Asian | 0.00891% | 11,220 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,496 |
| European (non-Finnish) | 0.00356% | 28,095 |
| Finnishnot grpmax-eligible | 0.00156% | 64,038 |
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.Pro838=
- Coding
- c.2514G>A
- MANE Select
- NM_014704
- dbSNP
- rs578262183
- Type
- single nucleotide variant
- Location
- chr1:3823231 (GRCh38)
- Gene constraint
- LOEUF 0.851 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.75 · 2 PDB
- Residue 838
- a UniProt-annotated variant site (in mrt77)
Similar variants
- CEP104 p.Pro838Leu 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-pro838 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown