CEP250 p.Ala642=
c.1926T>G · VCV4721346
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.014 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP 0.052 | GERP 1.1 |
| Overall | ||
| CADD | 6.257 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
South Asian · 2/89,828 alleles
Filtering AF
0.00037%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000138%
Overall
0.000137%
2/1,456,748 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
- CEP250
- Protein
- p.Ala642=
- Coding
- c.1926T>G
- MANE Select
- NM_007186
- Type
- single nucleotide variant
- Location
- chr20:35477933 (GRCh38)
- Gene constraint
- LOEUF 0.86 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.68 · 1 PDB
- Residue 642
- a UniProt-annotated variant site (in crdhl2); a UniProt-annotated variant site (in crdhl2; also found in a family with non-syndromic retinitis pigmentosa)
Similar variants
- CEP250 p.Arg1045Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1155Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1336Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1343Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1499Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1695Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg1869Ter Pathogenic/Likely pathogenic ★★ same type
- CEP250 p.Arg188Ter Pathogenic ★★ 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/cep250-p-ala642 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown