TLE2 p.Ser713=
c.2139C>G · VCV3456841
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.024 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.096 | phastCons 0.75 |
| Overall | ||
| CADD | 3.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00111%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0009%
Overall
0.00167%
27/1,612,152 alleles · ultra-rare
exomes 19/1,460,022 · genomes 8/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,603 |
| European (non-Finnish) | 0.0017% | 58,959 |
| African / African-American | 0.00134% | 74,886 |
| South Asian | 0.0011% | 90,622 |
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.Ser713=
- Coding
- c.2139C>G
- MANE Select
- NM_003260
- Type
- single nucleotide variant
- Location
- chr19:2997941 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.40
Similar variants
- 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
- TLE2 p.Ala192Val 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-ser713 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown