TF p.Leu65=
c.195T>C · rs544064945 · VCV2777171
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -6.7 | GERP -4 |
| Overall | ||
| CADD | 0.748 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,072 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.000682%
11/1,614,056 alleles · very rare
exomes 9/1,461,880 · genomes 2/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,179 |
| European (non-Finnish) | 0.000424% | 236,001 |
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.Leu65=
- Coding
- c.195T>C
- MANE Select
- NM_001063
- dbSNP
- rs544064945
- Type
- single nucleotide variant
- Location
- chr3:133748563 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.39 · 69 PDB
- Residue 65
- the transferrin-like 1 domain; an α-helix
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-leu65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown