Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 5.19%, afr) — 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 0.65 | GERP -3.1, phastCons 0.98 |
| Overall | ||
| CADD | 6.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.19%
African / African-American · 2,968/57,175 alleles
Filtering AF
5.04%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.97%
Overall
0.273%
3,300/1,210,044 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.19% | 19 |
| Remaining individualsnot grpmax-eligible | 0.359% | 278 |
| Admixed American | 0.286% | 350 |
| Middle Eastern | 0.253% | 396 |
| South Asian | 0.00881% | 11,354 |
| European (non-Finnish) | 0.00156% | 63,943 |
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
- APEX2
- Protein
- p.Ala309=
- Coding
- c.927A>G
- MANE Select
- NM_014481
- dbSNP
- rs6651872
- Type
- single nucleotide variant
- Location
- chrX:55006805 (GRCh38)
- Structure
- AlphaFold pLDDT 78.87
Similar variants
- APEX2 p.Ala83= Benign ★★ same type
- APEX2 p.Arg141Cys Likely benign ★★ same type
- APEX2 p.Ala126Ser Uncertain significance ★ ⚠ same type
- APEX2 p.Ala160Val Uncertain significance ★ ⚠ same type
- APEX2 p.Ala267Thr Uncertain significance ★ ⚠ same type
- APEX2 p.Ala29Ser Uncertain significance ★ ⚠ same type
- APEX2 p.Ala372Gly Uncertain significance ★ ⚠ same type
- APEX2 p.Arg125Trp 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/apex2-p-ala309 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown