TMPO p.Asn296Ser
c.887A>G · rs771589075 · VCV191796
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.094 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.1 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 3,511 bp · p 0.089 · regional, not allelic |
| Overall | ||
| CADD | 20.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
Middle Eastern · 1/5,350 alleles
Filtering AF
0.000954%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000787%
Overall
0.00161%
26/1,611,858 alleles · ultra-rare
exomes 21/1,459,712 · genomes 5/152,146 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0187% | 5,350 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,791 |
| East Asian | 0.00446% | 22,421 |
| European (non-Finnish) | 0.00153% | 65,501 |
| African / African-American | 0.00134% | 74,858 |
| South Asian | 0.0011% | 91,022 |
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.Asn296Ser
- Coding
- c.887A>G
- MANE Select
- NM_001032283
- dbSNP
- rs771589075
- Type
- single nucleotide variant
- Location
- chr12:98544958 (GRCh38)
- Gene constraint
- LOEUF 0.736 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.49 · 14 PDB
- Residue 296
- 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-asn296ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown