CTBP1 p.Cys226=
c.678C>T · rs374344295 · VCV2178599
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.104 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.98 | GERP -3.7, phastCons 1 |
| Overall | ||
| CADD | 15.12 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/75,008 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00379%
61/1,611,568 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,334 |
| European (non-Finnish) | 0.00398% | 25,103 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,154 |
| South Asian | 0.0022% | 45,470 |
| Finnishnot grpmax-eligible | 0.00157% | 63,582 |
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
- CTBP1
- Protein
- p.Cys226=
- Coding
- c.678C>T
- MANE Select
- NM_001012614
- dbSNP
- rs374344295
- Type
- single nucleotide variant
- Location
- chr4:1216042 (GRCh38)
- Gene constraint
- LOEUF 0.533 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 84.08 · 11 PDB
- Residue 226
- an α-helix
Similar variants
- CTBP1 p.Arg331Trp Pathogenic ★★ ⚠ same type
- CTBP1 c.-205C>G Uncertain significance ★★ ⚠ same type
- CTBP1 p.Ala384Pro Uncertain significance ★★ ⚠ same type
- CTBP1 p.Ala404Val Uncertain significance ★★ ⚠ same type
- CTBP1 p.Arg173Cys Uncertain significance ★★ ⚠ same type
- CTBP1 p.Gln137His Uncertain significance ★★ ⚠ same type
- CTBP1 p.Gly399Ser Uncertain significance ★★ ⚠ same type
- CTBP1 p.Pro292Ser 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/ctbp1-p-cys226 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown