TBL2 p.Ala189=
c.567G>A · rs141209031 · VCV788784
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.874%, mid)
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 -3.7 |
| Overall | ||
| CADD | 4.99 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.874%
Middle Eastern · 53/6,062 alleles
Filtering AF
0.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.771%
Overall
0.38%
6,140/1,614,192 alleles · rare
exomes 5,601/1,461,864 · genomes 539/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.874% | 114 |
| South Asian | 0.84% | 119 |
| Finnishnot grpmax-eligible | 0.679% | 147 |
| European (non-Finnish) | 0.377% | 266 |
| Remaining individualsnot grpmax-eligible | 0.331% | 302 |
| Admixed American | 0.245% | 408 |
| Ashkenazi Jewishnot grpmax-eligible | 0.142% | 705 |
| African / African-American | 0.0613% | 1,632 |
| East Asian | 0.00446% | 22,443 |
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
- TBL2
- Protein
- p.Ala189=
- Coding
- c.567G>A
- MANE Select
- NM_012453
- dbSNP
- rs141209031
- Type
- single nucleotide variant
- Location
- chr7:73573351 (GRCh38)
- Gene constraint
- LOEUF 1.054 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.11
Similar variants
- TBL2 p.Ala189Val Uncertain significance ★ ⚠ same residue
- TBL2 p.Ala332= Benign/Likely benign ★★ same type
- TBL2 p.Gln229= Benign ★★ same type
- TBL2 p.Glu135= Benign ★★ same type
- TBL2 p.Glu257Ala Benign ★★ same type
- TBL2 c.599-7C>A Uncertain significance ★ same type
- TBL2 p.Ala139Thr Uncertain significance ★ ⚠ same type
- TBL2 p.Ala139Val 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/tbl2-p-ala189 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown