TLE6 p.Ser561=
c.1683C>T · VCV3456880
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0252%, 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 -4.8 | |
| Overall | ||
| CADD | 4.519 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0252%
Admixed American · 15/59,568 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0125%
Overall
0.00218%
35/1,608,934 alleles · ultra-rare
exomes 30/1,456,918 · genomes 5/152,016 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0252% | 3,971 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,116 |
| Finnishnot grpmax-eligible | 0.00316% | 31,608 |
| African / African-American | 0.00267% | 37,402 |
| European (non-Finnish) | 0.00119% | 84,157 |
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.Ser561=
- Coding
- c.1683C>T
- MANE Select
- NM_001143986
- Type
- single nucleotide variant
- Location
- chr19:2994968 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.29 · 4 PDB
- Residue 561
- a UniProt-annotated variant site (in ozema15; uncertain significance); 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 p.Val429= Benign ★★ same type
- TLE6 c.741-1G>C 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-ser561 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown