TMPO p.Arg373=
c.1119G>A · rs144913822 · VCV165477
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.265%, afr)
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 0.6 | GERP -2.9, phastCons 0.99 |
| Overall | ||
| CADD | 6.342 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.265%
African / African-American · 199/75,028 alleles
Filtering AF
0.235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.223%
Overall
0.0152%
246/1,614,178 alleles · rare
exomes 123/1,461,878 · genomes 123/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.265% | 377 |
| Admixed American | 0.035% | 2,858 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,808 |
| South Asian | 0.00659% | 15,181 |
| East Asian | 0.00223% | 44,892 |
| European (non-Finnish) | 0.000508% | 196,673 |
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.Arg373=
- Coding
- c.1119G>A
- MANE Select
- NM_001032283
- dbSNP
- rs144913822
- Type
- single nucleotide variant
- Location
- chr12:98547612 (GRCh38)
- Gene constraint
- LOEUF 0.736 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.49 · 14 PDB
- Residue 373
- the 'nakap95-binding c' region; 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-arg373 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown