CEP250 p.Leu657=
c.1971G>A · rs373519159 · VCV1165107
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0534%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.028 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.74 | GERP -4.3, phastCons 0.001 |
| Overall | ||
| CADD | 2.588 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0534%
Admixed American · 32/59,958 alleles
Filtering AF
0.0388%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0339%
Overall
0.00936%
151/1,613,648 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0534% | 1,874 |
| Middle Eastern | 0.0493% | 2,027 |
| African / African-American | 0.0414% | 2,417 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,499 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0304% | 3,286 |
| European (non-Finnish) | 0.00424% | 23,598 |
| South Asian | 0.0011% | 90,940 |
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.Leu657=
- Coding
- c.1971G>A
- MANE Select
- NM_007186
- dbSNP
- rs373519159
- Type
- single nucleotide variant
- Location
- chr20:35477978 (GRCh38)
- Gene constraint
- LOEUF 0.86 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.68 · 1 PDB
- Residue 657
- 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-leu657 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown