TBR1 p.Pro69=
c.207T>C · VCV4957140
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 6.2 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 14.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,024 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000558%
9/1,614,216 alleles · very rare
exomes 9/1,461,892 · genomes 0/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,024 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| European (non-Finnish) | 0.000593% | 168,576 |
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
- TBR1
- Protein
- p.Pro69=
- Coding
- c.207T>C
- MANE Select
- NM_006593
- Type
- single nucleotide variant
- Location
- chr2:161416617 (GRCh38)
- Gene constraint
- LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.17
- Residue 69
- the 'disordered' region
Similar variants
- TBR1 c.1190+1G>A Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Arg392Trp Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Gln282Ter Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Gln373Arg Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Trp271Arg Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Trp299Ter Pathogenic/Likely pathogenic ★★ same type
- TBR1 p.Ala187Pro Uncertain significance ★★ ⚠ same type
- TBR1 p.Arg424His 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/tbr1-p-pro69 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown