TLE2 p.Ser709=
c.2127C>T · VCV3456849
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
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 0.21 | phastCons 0.51 |
| Overall | ||
| CADD | 4.982 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,792 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000249%
4/1,608,150 alleles · very rare
exomes 2/1,456,058 · genomes 2/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,931 |
| European (non-Finnish) | 8.5e-05% | 1,176,406 |
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
- TLE2
- Protein
- p.Ser709=
- Coding
- c.2127C>T
- MANE Select
- NM_003260
- Type
- single nucleotide variant
- Location
- chr19:2997953 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.40
Similar variants
- TLE2 p.Ser709Phe Uncertain significance ★ ⚠ same residue
- TLE2 p.Ala110Thr Uncertain significance ★ ⚠ same type
- TLE2 p.Ala133Val Uncertain significance ★ ⚠ same type
- TLE2 p.Ala164Val Uncertain significance ★ ⚠ same type
- TLE2 p.Ala167Val Uncertain significance ★ ⚠ same type
- TLE2 p.Ala168Val Uncertain significance ★ ⚠ same type
- TLE2 p.Ala187Ser Uncertain significance ★ ⚠ same type
- TLE2 p.Ala187Val 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/tle2-p-ser709 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown