TET3 p.Pro457=
c.1371C>T · rs61742889 · VCV1288297
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 15.7%, amr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.8 |
| Overall | ||
| CADD | 0.597 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
15.7%
Admixed American · 9,442/60,024 alleles
Filtering AF
15.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 15.4%
Overall
0.615%
9,925/1,614,028 alleles · common
exomes 8,363/1,461,684 · genomes 1,562/152,344 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 15.7% | 6 |
| Remaining individualsnot grpmax-eligible | 0.451% | 222 |
| African / African-American | 0.18% | 556 |
| European (non-Finnish) | 0.00551% | 18,152 |
| East Asian | 0.00223% | 44,868 |
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
- TET3
- Protein
- p.Pro457=
- Coding
- c.1371C>T
- MANE Select
- NM_001287491
- dbSNP
- rs61742889
- Type
- single nucleotide variant
- Location
- chr2:74047288 (GRCh38)
- Gene constraint
- LOEUF 0.213 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 52.49 · 2 PDB
- Residue 457
- the 'disordered' region
Similar variants
- TET3 p.Arg1034Ter Pathogenic/Likely pathogenic ★★ same type
- TET3 p.Arg1150Ter Pathogenic ★★ same type
- TET3 p.Arg911Gln Likely pathogenic ★★ same type
- TET3 p.Arg1054His Uncertain significance ★★ ⚠ same type
- TET3 p.Arg1688Cys Uncertain significance ★★ ⚠ same type
- TET3 p.Arg1744His Uncertain significance ★★ ⚠ same type
- TET3 p.Arg430Gly Uncertain significance ★★ ⚠ same type
- TET3 p.Arg604Gln 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/tet3-p-pro457 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown