TSFM p.Leu289fs
c.866dup · VCV3725184
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.1 | GERP 2.3, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- TSFM
- Protein
- p.Leu289fs
- Coding
- c.866dup
- MANE Select
- NM_005726
- Type
- Duplication
- Location
- chr12:57796468 (GRCh38)
- Gene constraint
- LOEUF 1.197 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.87 · 1 PDB
- Residue 289
- a UniProt-annotated variant site (in coxpd3)
Similar variants
- TSFM p.Leu289Phe Uncertain significance ★ ⚠ same residue
- TSFM p.Leu289= Likely benign ★ same residue
- TSFM p.Ala13fs Pathogenic/Likely pathogenic ★★ same type
- TSFM p.Arg201fs Pathogenic/Likely pathogenic ★★ same type
- TSFM c.484-1003_484-1000dup Likely pathogenic ★ same type
- TSFM p.Arg39fs Likely pathogenic ★ same type
- TSFM p.Leu118fs Pathogenic ★ same type
- TSFM p.Leu11fs 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/tsfm-p-leu289fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown