TF p.Leu513=
c.1539C>G · rs1034506993 · VCV721529
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
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 0.25 | GERP 0.95, phastCons 0.98 |
| Overall | ||
| CADD | 3.945 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/60,010 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00161%
26/1,614,106 alleles · ultra-rare
exomes 20/1,461,880 · genomes 6/152,226 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,616 |
| Middle Eastern | 0.0164% | 6,084 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,828 |
| European (non-Finnish) | 0.000763% | 131,117 |
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
- TF
- Protein
- p.Leu513=
- Coding
- c.1539C>G
- MANE Select
- NM_001063
- dbSNP
- rs1034506993
- Type
- single nucleotide variant
- Location
- chr3:133768081 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.39 · 69 PDB
- Residue 513
- an α-helix; the transferrin-like 2 domain
Similar variants
- TF c.-18C>T Uncertain significance ★★ same type
- TF p.Ala318Ser Uncertain significance ★★ ⚠ same type
- TF p.Ala72Val Uncertain significance ★★ ⚠ same type
- TF p.Gln264Glu Uncertain significance ★★ ⚠ same type
- TF p.Gln559Leu Uncertain significance ★★ ⚠ same type
- TF p.Ile229Thr Uncertain significance ★★ ⚠ same type
- TF p.Thr112Ala Uncertain significance ★★ ⚠ same type
- TF p.Val270Asp Uncertain significance ★★ ⚠ 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/tf-p-leu513 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown