TF p.Ala181=
c.543G>A · rs765159608 · VCV2895250
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, 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 -1.7 | GERP -4.1 |
| Overall | ||
| CADD | 5.753 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,026 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000619%
10/1,614,224 alleles · very rare
exomes 10/1,461,892 · genomes 0/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,009 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| East Asian | 0.00223% | 44,886 |
| European (non-Finnish) | 0.000339% | 295,011 |
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.Ala181=
- Coding
- c.543G>A
- MANE Select
- NM_001063
- dbSNP
- rs765159608
- Type
- single nucleotide variant
- Location
- chr3:133755403 (GRCh38)
- Gene constraint
- LOEUF 0.834 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.39 · 69 PDB
- Residue 181
- the transferrin-like 1 domain
Similar variants
- TF p.Ala181Val Uncertain significance ★ ⚠ same residue
- 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
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-ala181 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown