TBR1 p.Phe387=
c.1161T>C · rs181943543 · VCV778013
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, 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 2.3 | GERP 0.48, phastCons 1 |
| Overall | ||
| CADD | 11.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,060 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.00217%
35/1,613,682 alleles · ultra-rare
exomes 29/1,461,370 · genomes 6/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,030 |
| African / African-American | 0.0227% | 4,414 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,943 |
| European (non-Finnish) | 0.000593% | 168,545 |
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.Phe387=
- Coding
- c.1161T>C
- MANE Select
- NM_006593
- dbSNP
- rs181943543
- Type
- single nucleotide variant
- Location
- chr2:161420228 (GRCh38)
- Gene constraint
- LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 56.17
- Residue 387
- a DNA-binding 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-phe387 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown