TMIE p.Pro9=
c.27C>T · VCV4962104
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00229%, nfe)
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 -0.24 | GERP -0.034, phastCons 0.025 |
| Overall | ||
| CADD | 7.359 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00229%
European (non-Finnish) · 24/1,046,720 alleles
Filtering AF
0.00155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0013%
Overall
0.0018%
24/1,333,890 alleles · very rare
exomes 20/1,181,792 · genomes 4/152,098 · 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
- TMIE
- Protein
- p.Pro9=
- Coding
- c.27C>T
- MANE Select
- NM_147196
- Type
- single nucleotide variant
- Location
- chr3:46701514 (GRCh38)
- Gene constraint
- LOEUF 1.475 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 63.41
Similar variants
- TMIE p.Arg84Trp Likely pathogenic ★★ same type
- TMIE p.Glu31Gly Pathogenic/Likely pathogenic ★★ ⚠ same type
- TMIE c.-154G>A Uncertain significance ★★ same type
- TMIE c.*253G>A Uncertain significance ★★ same type
- TMIE p.Ala17Thr Uncertain significance ★★ ⚠ same type
- TMIE p.Ala2Gly Uncertain significance ★★ ⚠ same type
- TMIE p.Ala2Val Uncertain significance ★★ ⚠ same type
- TMIE p.Asn113Ser 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/tmie-p-pro9 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown