TLE6 p.Val429=
c.1287C>T · rs114814891 · VCV782318
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.47%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.36 | |
| Overall | ||
| CADD | 0.85 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.47%
African / African-American · 2,603/74,952 alleles
Filtering AF
3.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.32%
Overall
0.183%
2,947/1,613,820 alleles · low-frequency
exomes 1,418/1,461,844 · genomes 1,529/151,976 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.47% | 29 |
| Admixed American | 0.275% | 363 |
| Remaining individualsnot grpmax-eligible | 0.234% | 428 |
| Middle Eastern | 0.115% | 866 |
| South Asian | 0.00769% | 13,009 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| European (non-Finnish) | 0.00153% | 65,554 |
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
- TLE6
- Protein
- p.Val429=
- Coding
- c.1287C>T
- MANE Select
- NM_001143986
- dbSNP
- rs114814891
- Type
- single nucleotide variant
- Location
- chr19:2991885 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.29 · 4 PDB
- Residue 429
- a β-strand
Similar variants
- TLE6 p.Ala207Thr Uncertain significance ★★ ⚠ same type
- TLE6 c.1537+7G>A Benign ★★ same type
- TLE6 p.Glu287= Likely benign ★★ same type
- TLE6 p.His285= Benign ★★ same type
- TLE6 p.His564= Benign/Likely benign ★★ same type
- TLE6 p.Ser490= Benign ★★ same type
- TLE6 c.741-1G>C Likely pathogenic ★ same type
- TLE6 p.Gln383Ter 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/tle6-p-val429 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown