TLE6 p.Ser490=
c.1470C>T · rs10406955 · VCV777363
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 8.67%, afr) — too common for a highly-penetrant pathogenic allele
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 -13 | |
| Overall | ||
| CADD | 0.022 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.67%
African / African-American · 6,441/74,298 alleles
Filtering AF
8.49%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.42%
Overall
0.505%
8,049/1,593,360 alleles · common
exomes 4,233/1,441,118 · genomes 3,816/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 8.67% | 12 |
| South Asian | 0.709% | 141 |
| Remaining individualsnot grpmax-eligible | 0.582% | 172 |
| Admixed American | 0.516% | 194 |
| Middle Eastern | 0.233% | 428 |
| European (non-Finnish) | 0.0247% | 4,043 |
| East Asian | 0.00683% | 14,646 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00341% | 29,284 |
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.Ser490=
- Coding
- c.1470C>T
- MANE Select
- NM_001143986
- dbSNP
- rs10406955
- Type
- single nucleotide variant
- Location
- chr19:2993515 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.29 · 4 PDB
- Residue 490
- 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.Val429= 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-ser490 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown