ASTN2 p.Leu142=
c.426G>T · rs146304956 · VCV3044259
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.34%, afr)
Conditions
1
ASTN2-related disorder
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 2.1 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.34%
African / African-American · 254/74,630 alleles
Filtering AF
0.306%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.293%
Overall
0.0162%
261/1,609,168 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.34% | 294 |
| Admixed American | 0.00501% | 19,971 |
| Remaining individualsnot grpmax-eligible | 0.00483% | 20,725 |
| European (non-Finnish) | 8.49e-05% | 1,178,300 |
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
- ASTN2
- Protein
- p.Leu142=
- Coding
- c.426G>T
- MANE Select
- NM_001365068
- dbSNP
- rs146304956
- Type
- single nucleotide variant
- Location
- chr9:117414513 (GRCh38)
- Gene constraint
- LOEUF 0.473 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.93 · 3 PDB
Disease context
ASTN2-related disorder
Similar variants
- TRIM32 p.Ala142= Likely benign ★ same residue
- TRIM32 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same condition
- TRIM32 p.Asp487Asn Pathogenic ★★ same condition
- TRIM32 p.Tyr226Ter Pathogenic/Likely pathogenic ★★ same condition
- ASTN2 p.Val880Gly Uncertain significance ★★ ⚠ same condition
- TRIM32 p.Arg147Gln Uncertain significance ★★ ⚠ same condition
- TRIM32 p.Arg238Leu Uncertain significance ★★ ⚠ same condition
- TRIM32 p.Arg563Cys Uncertain significance ★★ ⚠ same condition
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/astn2-p-leu142 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown