ASTN2 p.Pro494=
c.1482G>A · rs3761845 · VCV1248446
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 75.7%, eas) — too common for a highly-penetrant pathogenic allele
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 -9.1 | GERP -3.2 |
| Overall | ||
| CADD | 3.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
75.7%
East Asian · 33,705/44,504 alleles
Filtering AF
75.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 74.8%
Overall
55.4%
891,793/1,609,010 alleles · common
exomes 820,377/1,457,012 · genomes 71,416/151,998 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 75.7% | 1 |
| Admixed American | 68.3% | 1 |
| Amishnot grpmax-eligible | 65.2% | 2 |
| European (non-Finnish) | 57.1% | 2 |
| Finnishnot grpmax-eligible | 56% | 2 |
| Remaining individualsnot grpmax-eligible | 54.7% | 2 |
| South Asian | 49.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 49.6% | 2 |
| Middle Eastern | 44.7% | 2 |
| African / African-American | 17.5% | 6 |
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.Pro494=
- Coding
- c.1482G>A
- MANE Select
- NM_001365068
- dbSNP
- rs3761845
- Type
- single nucleotide variant
- Location
- chr9:117008201 (GRCh38)
- Gene constraint
- LOEUF 0.473 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.93 · 3 PDB
Similar variants
- TRIM32 p.Trp494Ter Likely pathogenic ★ same residue
- ASTN2 p.Pro494Leu Uncertain significance ★ ⚠ same residue
- TRIM32 p.Arg500Ter Pathogenic/Likely pathogenic ★★ same type
- TRIM32 p.Asp487Asn Pathogenic ★★ same type
- TRIM32 p.Lys401Ter Pathogenic ★★ same type
- TRIM32 p.Tyr226Ter Pathogenic/Likely pathogenic ★★ same type
- TRIM32 p.Tyr528Ter Likely pathogenic ★★ same type
- ASTN2 p.Val880Gly 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/astn2-p-pro494 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown