ASTN2 p.Lys867=
c.2601G>A · rs761835705 · VCV708946
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.15%, mid)
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 -0.36 | GERP -3.4, phastCons 0.098 |
| Overall | ||
| CADD | 3.698 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.15%
Middle Eastern · 9/6,012 alleles
Filtering AF
0.0781%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0583%
Overall
0.00271%
43/1,585,410 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.15% | 668 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0207% | 4,836 |
| South Asian | 0.00574% | 17,407 |
| African / African-American | 0.00536% | 18,662 |
| Remaining individualsnot grpmax-eligible | 0.00326% | 30,682 |
| Admixed American | 0.00178% | 56,108 |
| European (non-Finnish) | 0.00137% | 72,793 |
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.Lys867=
- Coding
- c.2601G>A
- MANE Select
- NM_001365068
- dbSNP
- rs761835705
- Type
- single nucleotide variant
- Location
- chr9:116729017 (GRCh38)
- Gene constraint
- LOEUF 0.473 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.93 · 3 PDB
- Residue 867
- a disulfide bond; a β-strand
Similar variants
- 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
- TRIM32 c.*152T>G Uncertain significance ★★ same type
- TRIM32 p.Ala126Val 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-lys867 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown