TLE2 p.Tyr68=
c.204C>T · VCV3326292
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
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 -2.5 | |
| Overall | ||
| CADD | 0.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,650 alleles
Filtering AF
0.00546%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00382%
Overall
0.0013%
21/1,611,234 alleles · ultra-rare
exomes 17/1,459,106 · genomes 4/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0117% | 8,521 |
| African / African-American | 0.00668% | 14,970 |
| South Asian | 0.00555% | 18,021 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,416 |
| European (non-Finnish) | 0.000254% | 392,986 |
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.Tyr68=
- Coding
- c.204C>T
- MANE Select
- NM_003260
- Type
- single nucleotide variant
- Location
- chr19:3027856 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.40
- Residue 68
- the 'q domain' region
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-tyr68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown