TSFM p.Leu289Phe
c.867G>C · VCV4633817
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.4733 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| AlphaMissense | 0.4733 | ambiguous |
|---|---|---|
| REVEL | 0.703 | pathogenic-leaning |
| SaProt | LLR -6.45 | tolerated |
| ⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.7 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 3,578 bp · p 0.37 · regional, not allelic |
| Overall | ||
| CADD | 24.2 | 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
- TSFM
- Protein
- p.Leu289Phe
- Coding
- c.867G>C
- MANE Select
- NM_005726
- Type
- single nucleotide variant
- Location
- chr12:57796472 (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.Leu289= Likely benign ★ same residue
- TSFM p.Ala174Val Uncertain significance ★★ ⚠ same condition
- TSFM p.Ala20Val Uncertain significance ★★ ⚠ same condition
- TSFM p.Ala220Thr Uncertain significance ★★ ⚠ same condition
- TSFM p.Ala264Asp Uncertain significance ★★ ⚠ same condition
- TSFM p.Arg255Cys Uncertain significance ★★ ⚠ same condition
- TSFM p.Arg255His Uncertain significance ★★ ⚠ same condition
- TSFM p.Arg31Thr Uncertain significance ★★ ⚠ same condition
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-leu289phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown