TLE6 p.Asn77=
c.231C>T · VCV4821543
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0392%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.31 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.23 | gain · loss 0.21 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.39 | |
| Overall | ||
| CADD | 14.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0392%
Admixed American · 20/50,984 alleles
Filtering AF
0.0259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0217%
Overall
0.0149%
231/1,551,704 alleles · ultra-rare
exomes 212/1,399,416 · genomes 19/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0392% | 2,549 |
| European (non-Finnish) | 0.0173% | 5,793 |
| Remaining individualsnot grpmax-eligible | 0.00998% | 10,019 |
| African / African-American | 0.00683% | 14,632 |
| East Asian | 0.00244% | 40,924 |
| South Asian | 0.00119% | 84,068 |
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.Asn77=
- Coding
- c.231C>T
- MANE Select
- NM_001143986
- Type
- single nucleotide variant
- Location
- chr19:2986837 (GRCh38)
- Gene constraint
- LOEUF 1.121 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 66.29 · 4 PDB
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.Ser490= Benign ★★ same type
- TLE6 p.Val429= Benign ★★ same type
- TLE6 c.741-1G>C 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-asn77 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown