CCBE1 p.Arg118=
c.354A>G · rs116239086 · VCV731478
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.51 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.56 | gain · loss 0.19 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -4.9 |
| Overall | ||
| CADD | 13.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
African / African-American · 101/75,034 alleles
Filtering AF
0.113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.105%
Overall
0.0133%
214/1,614,158 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.135% | 743 |
| Middle Eastern | 0.0661% | 1,513 |
| Admixed American | 0.0183% | 5,457 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,251 |
| European (non-Finnish) | 0.00746% | 13,409 |
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.Arg118=
- Coding
- c.354A>G
- MANE Select
- NM_133459
- dbSNP
- rs116239086
- Type
- single nucleotide variant
- Location
- chr18:59469519 (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.Arg118Ter Pathogenic/Likely pathogenic ★★ same residue
- CCBE1 p.Arg118Gln Uncertain significance ★ ⚠ same residue
- CCBE1 p.Arg118Leu Uncertain significance ★ ⚠ same residue
- CCBE1 p.Arg108Ter 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
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-arg118 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown