TMPO p.Arg269His
c.806G>A · rs142891873 · VCV165476
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0387%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.056 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP -1.2, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 3,511 bp · p 0.089 · regional, not allelic |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0387%
African / African-American · 29/74,866 alleles
Filtering AF
0.0277%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0239%
Overall
0.00632%
102/1,613,682 alleles · ultra-rare
exomes 78/1,461,622 · genomes 24/152,060 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0387% | 2,582 |
| Admixed American | 0.00667% | 14,995 |
| European (non-Finnish) | 0.00509% | 19,665 |
| Finnishnot grpmax-eligible | 0.00469% | 21,335 |
| South Asian | 0.00329% | 30,351 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,234 |
| East Asian | 0.00223% | 44,844 |
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.Arg269His
- Coding
- c.806G>A
- MANE Select
- NM_001032283
- dbSNP
- rs142891873
- Type
- single nucleotide variant
- Location
- chr12:98544464 (GRCh38)
- Gene constraint
- LOEUF 0.736 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.49 · 14 PDB
- Residue 269
- 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-arg269his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown