TF p.Ile397=
c.1191C>T · rs776533532 · VCV2965661
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, 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 -3.1 | GERP -3.8 |
| Overall | ||
| CADD | 9.885 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0188%
Overall
0.00242%
39/1,613,430 alleles · ultra-rare
exomes 37/1,461,512 · genomes 2/151,918 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| South Asian | 0.0307% | 3,252 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| Finnishnot grpmax-eligible | 0.00157% | 63,666 |
| European (non-Finnish) | 0.000254% | 393,323 |
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.Ile397=
- Coding
- c.1191C>T
- MANE Select
- NM_001063
- dbSNP
- rs776533532
- Type
- single nucleotide variant
- Location
- chr3:133759317 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.39 · 69 PDB
- Residue 397
- 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-ile397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown