ANKLE2 p.Ala712=
c.2136G>A · rs762852125 · VCV3061493
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00401%, afr)
Conditions
1
ANKLE2-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 -2.5 | |
| Overall | ||
| CADD | 2.776 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00401%
African / African-American · 3/74,898 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000558%
9/1,613,092 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00401% | 24,966 |
| South Asian | 0.0011% | 91,078 |
| European (non-Finnish) | 0.000424% | 235,983 |
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
- ANKLE2
- Protein
- p.Ala712=
- Coding
- c.2136G>A
- MANE Select
- NM_015114
- dbSNP
- rs762852125
- Type
- single nucleotide variant
- Location
- chr12:132730026 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 712
- a UniProt-annotated variant site (in mcph16; uncertain significance)
Disease context
ANKLE2-related disorder
Similar variants
- ANKLE2 c.*8G>A Likely benign same condition
- ANKLE2 p.Gly700= Likely benign same condition
- ANKLE2 p.His671Tyr Likely benign same condition
- ANKLE2 p.Pro664= Likely benign same condition
- ANKLE2 p.Pro910= Likely benign same condition
- ANKLE2 c.1892-11_1892-9del Likely benign same condition
- ANKLE2 p.Arg624Ter Pathogenic ★★ same type
- ANKLE2 p.Arg99Ser 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/ankle2-p-ala712 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown