TLE2 p.Ser228=
c.684C>T · rs199912249 · VCV2648982
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.133%, mid)
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 -2.7 | |
| Overall | ||
| CADD | 2.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.133%
Middle Eastern · 8/5,994 alleles
Filtering AF
0.0663%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0484%
Overall
0.035%
556/1,588,780 alleles · rare
exomes 509/1,436,538 · genomes 47/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.133% | 749 |
| Finnishnot grpmax-eligible | 0.118% | 847 |
| Remaining individualsnot grpmax-eligible | 0.0572% | 1,749 |
| European (non-Finnish) | 0.0346% | 2,889 |
| South Asian | 0.023% | 4,357 |
| Admixed American | 0.0175% | 5,719 |
| African / African-American | 0.00541% | 18,470 |
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.Ser228=
- Coding
- c.684C>T
- MANE Select
- NM_003260
- dbSNP
- rs199912249
- Type
- single nucleotide variant
- Location
- chr19:3014609 (GRCh38)
- Gene constraint
- LOEUF 1.02 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 68.40
- Residue 228
- the 'ccn domain' region; a modified residue (phosphoserine; by ck2); the 'disordered' 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-ser228 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown