TPX2 p.Leu491=
c.1471T>C · rs746729105 · VCV2652251
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.6 | GERP -5.3 |
| Overall | ||
| CADD | 0.757 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,898 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00112%
18/1,614,088 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,898 |
| European (non-Finnish) | 0.00136% | 73,752 |
| African / African-American | 0.00133% | 74,932 |
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
- TPX2
- Protein
- p.Leu491=
- Coding
- c.1471T>C
- MANE Select
- NM_012112
- dbSNP
- rs746729105
- Type
- single nucleotide variant
- Location
- chr20:31792792 (GRCh38)
- Gene constraint
- LOEUF 0.29 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.23 · 14 PDB
Similar variants
- TPX2 p.Ala184= Benign ★★ same type
- TPX2 p.Ser94= Benign ★★ same type
- TPX2 p.Ala142Val Uncertain significance ★ ⚠ same type
- TPX2 p.Ala184Gly Uncertain significance ★ ⚠ same type
- TPX2 p.Ala668Val Uncertain significance ★ ⚠ same type
- TPX2 p.Ala683Pro Uncertain significance ★ ⚠ same type
- TPX2 p.Arg229Trp Uncertain significance ★ ⚠ same type
- TPX2 p.Arg267Gln 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/tpx2-p-leu491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown