Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.5%, 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 -0.5 | GERP -4.2, phastCons 0.11 |
| Overall | ||
| CADD | 10.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.5%
African / African-American · 1,123/75,022 alleles
Filtering AF
1.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.39%
Overall
0.0926%
1,495/1,614,046 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.5% | 67 |
| Middle Eastern | 0.33% | 303 |
| Ashkenazi Jewishnot grpmax-eligible | 0.166% | 604 |
| Admixed American | 0.163% | 612 |
| Remaining individualsnot grpmax-eligible | 0.125% | 801 |
| European (non-Finnish) | 0.0101% | 9,916 |
| Finnishnot grpmax-eligible | 0.00781% | 12,804 |
| South Asian | 0.00329% | 30,361 |
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
- CTNNB1
- Protein
- p.Ile140=
- Coding
- c.420T>C
- MANE Select
- NM_001904
- dbSNP
- rs3856746
- Type
- single nucleotide variant
- Location
- chr3:41225132 (GRCh38)
- Gene constraint
- LOEUF 0.139 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.02 · 50 PDB
Similar variants
- CTNNB1 p.Ile140fs Pathogenic ★★ same residue
- CTNNB1 c.1081+1G>T Pathogenic/Likely pathogenic ★★ same type
- CTNNB1 c.1082-1G>C Pathogenic ★★ same type
- CTNNB1 c.735-1G>C Pathogenic ★★ same type
- CTNNB1 p.Arg474Ter Pathogenic ★★ same type
- CTNNB1 p.Arg515Ter Pathogenic ★★ same type
- CTNNB1 p.Arg535Ter Pathogenic ★★ same type
- CTNNB1 p.Arg587Ter Pathogenic/Likely 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/ctnnb1-p-ile140 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown