CEP89 p.Ala291=
c.873G>A · rs138753622 · VCV1588608
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0475%, nfe)
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 -7.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.202 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0475%
European (non-Finnish) · 561/1,179,828 alleles
Filtering AF
0.0442%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.043%
Overall
0.0387%
624/1,613,616 alleles · ultra-rare
exomes 582/1,461,292 · genomes 42/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0475% | 2,103 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,975 |
| Middle Eastern | 0.033% | 3,031 |
| African / African-American | 0.0267% | 3,750 |
| Admixed American | 0.015% | 6,659 |
| South Asian | 0.0077% | 12,990 |
| East Asian | 0.00668% | 14,961 |
| Finnishnot grpmax-eligible | 0.00156% | 63,980 |
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
- CEP89
- Protein
- p.Ala291=
- Coding
- c.873G>A
- MANE Select
- NM_032816
- dbSNP
- rs138753622
- Type
- single nucleotide variant
- Location
- chr19:32933464 (GRCh38)
- Gene constraint
- LOEUF 1.173 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.08
Similar variants
- CEP89 p.Ala291Thr Uncertain significance ★★ ⚠ same residue
- CEP89 p.Ala291Val Uncertain significance ★★ ⚠ same residue
- CEP89 p.Ala372Thr Uncertain significance ★★ ⚠ same type
- CEP89 p.Ala54Val Uncertain significance ★★ ⚠ same type
- CEP89 p.Ala680Thr Uncertain significance ★★ ⚠ same type
- CEP89 p.Ala780Asp Uncertain significance ★★ ⚠ same type
- CEP89 p.Arg102Trp Uncertain significance ★★ ⚠ same type
- CEP89 p.Arg324Cys Uncertain significance ★★ ⚠ same type
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/cep89-p-ala291 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown