TNC p.Leu136=
c.408G>A · rs140689506 · VCV425458
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0331%, mid)
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 1.1 | phastCons 0.9 |
| Overall | ||
| CADD | 6.044 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0331%
Middle Eastern · 2/6,044 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00243%
Overall
0.000561%
9/1,604,080 alleles · ultra-rare
exomes 7/1,451,846 · genomes 2/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0331% | 3,022 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,076 |
| South Asian | 0.00112% | 89,194 |
| European (non-Finnish) | 0.000426% | 234,893 |
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
- TNC
- Protein
- p.Leu136=
- Coding
- c.408G>A
- MANE Select
- NM_002160
- dbSNP
- rs140689506
- Type
- single nucleotide variant
- Location
- chr9:115090611 (GRCh38)
- Gene constraint
- LOEUF 0.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.48 · 21 PDB
Similar variants
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- TNC p.Arg669His Uncertain significance ★★ ⚠ same type
- TNC p.Arg747Trp Uncertain significance ★★ ⚠ same type
- TNC p.Asn507Lys Uncertain significance ★★ ⚠ same type
- TNC p.Asp2059Glu Uncertain significance ★★ ⚠ same type
- TNC p.Asp831Asn Uncertain significance ★★ ⚠ same type
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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/tnc-p-leu136 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown