CCBE1 p.Leu239=
c.717G>A · rs377162045 · VCV2781292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
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 3.2 | GERP 0.47, phastCons 1 |
| Overall | ||
| CADD | 11.67 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,928 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.00031%
5/1,614,056 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,976 |
| European (non-Finnish) | 0.000169% | 590,023 |
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
- CCBE1
- Protein
- p.Leu239=
- Coding
- c.717G>A
- MANE Select
- NM_133459
- dbSNP
- rs377162045
- Type
- single nucleotide variant
- Location
- chr18:59448041 (GRCh38)
- Gene constraint
- LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 65.61
Similar variants
- CCBE1 p.Arg108Ter Pathogenic ★★ same type
- CCBE1 p.Arg118Ter Pathogenic/Likely pathogenic ★★ same type
- CCBE1 c.654+5G>C Uncertain significance ★★ same type
- CCBE1 c.*203A>G Uncertain significance ★★ same type
- CCBE1 c.*4173A>G Uncertain significance ★★ same type
- CCBE1 p.Ala28Val Uncertain significance ★★ ⚠ same type
- CCBE1 p.Ala322Val Uncertain significance ★★ ⚠ same type
- CCBE1 p.Ala96Gly 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/ccbe1-p-leu239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown