TMPO p.His44=
c.132C>T · rs957566846 · VCV1770099
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 19.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Overall
0.000248%
4/1,612,010 alleles · ultra-rare
exomes 4/1,459,680 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| East Asian | 0.00223% | 44,846 |
| African / African-American | 0.00133% | 75,046 |
| European (non-Finnish) | 8.48e-05% | 1,179,697 |
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
- TMPO
- Protein
- p.His44=
- Coding
- c.132C>T
- MANE Select
- NM_001032283
- dbSNP
- rs957566846
- Type
- single nucleotide variant
- Location
- chr12:98515999 (GRCh38)
- Gene constraint
- LOEUF 0.736 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.49 · 14 PDB
- Residue 44
- the lem-like domain; a β-strand; the 'nucleoplasmic' region
Similar variants
- TMPO c.565+1005A>G Uncertain significance ★★ ⚠ same type
- TMPO c.565+1009T>C Uncertain significance ★★ ⚠ same type
- TMPO c.565+1012A>C Uncertain significance ★★ ⚠ same type
- TMPO c.565+1017A>G Uncertain significance ★★ ⚠ same type
- TMPO c.565+1026A>G Uncertain significance ★★ ⚠ same type
- TMPO c.565+1029G>T Uncertain significance ★★ ⚠ same type
- TMPO c.565+1048G>C Uncertain significance ★★ ⚠ same type
- TMPO c.565+1053A>G 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/tmpo-p-his44 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown