TMPO p.Met348Ile
c.1044G>C · VCV3390642
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000339%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.168 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 0.89 | unconstrained · MANE · 3,511 bp · p 0.089 · regional, not allelic |
| Overall | ||
| CADD | 24.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000339%
European (non-Finnish) · 4/1,178,384 alleles
Filtering AF
7.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000248%
4/1,611,884 alleles · very rare
exomes 4/1,460,150 · genomes 0/151,734 · joint denominator
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.Met348Ile
- Coding
- c.1044G>C
- MANE Select
- NM_001032283
- Type
- single nucleotide variant
- Location
- chr12:98546412 (GRCh38)
- Gene constraint
- LOEUF 0.736 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.49 · 14 PDB
- Residue 348
- the 'disordered' region; the 'binds lamins b' region; the 'nakap95-binding c' region; the 'nucleoplasmic' region
Similar variants
- TMPO p.Met348Val Uncertain significance ★ same residue
- 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
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-met348ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown