ANKLE2 p.Pro910=
c.2730A>G · rs2043718849 · VCV3055782
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00136%, 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 -2.1 | |
| Overall | ||
| CADD | 0.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
African / African-American · 1/73,668 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000192%
3/1,563,040 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00136% | 73,668 |
| European (non-Finnish) | 0.000173% | 577,107 |
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.Pro910=
- Coding
- c.2730A>G
- MANE Select
- NM_015114
- dbSNP
- rs2043718849
- Type
- single nucleotide variant
- Location
- chr12:132727329 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 910
- a UniProt-annotated variant site (in mcph16; uncertain significance); a UniProt-annotated variant site (in mcph16); the 'disordered' region
Disease context
ANKLE2-related disorder
Similar variants
- ANKLE2 c.*8G>A Likely benign same condition
- ANKLE2 p.Ala712= 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 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-pro910 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown