TLE6 p.Ser343Pro
c.1027T>C · VCV4185037
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4497 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
0/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4497 | ambiguous |
|---|---|---|
| REVEL | 0.063 | moderately benign-leaning |
| SaProt | LLR -9.77 | tolerated |
| ⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -3.7 | |
| Regional constraint | o/e 1.13 | unconstrained · MANE · 17 kb · p 0.00048 · regional, not allelic |
| Overall | ||
| CADD | 14.72 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TLE6
- Protein
- p.Ser343Pro
- Coding
- c.1027T>C
- MANE Select
- NM_001143986
- Type
- single nucleotide variant
- Location
- chr19:2989568 (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-ser343pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown