ANKLE2 p.Ala688=
c.2064C>T · rs545290587 · VCV710856
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, afr)
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 1.6 | phastCons 0.91 |
| Overall | ||
| CADD | 10.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
African / African-American · 20/75,012 alleles
Filtering AF
0.0177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0147%
Overall
0.00434%
70/1,612,404 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0267% | 3,751 |
| Remaining individualsnot grpmax-eligible | 0.0208% | 4,805 |
| Admixed American | 0.005% | 19,998 |
| East Asian | 0.00446% | 22,429 |
| South Asian | 0.00439% | 22,766 |
| European (non-Finnish) | 0.00237% | 42,130 |
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.Ala688=
- Coding
- c.2064C>T
- MANE Select
- NM_015114
- dbSNP
- rs545290587
- Type
- single nucleotide variant
- Location
- chr12:132730098 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 688
- a UniProt-annotated variant site (in mcph16; uncertain significance)
Similar variants
- ANKLE2 p.Arg624Ter Pathogenic ★★ same type
- ANKLE2 p.Arg99Ser Uncertain significance ★★ ⚠ same type
- ANKLE2 p.Asn633His Uncertain significance ★★ ⚠ same type
- ANKLE2 p.Asn660Ile Uncertain significance ★★ ⚠ same type
- ANKLE2 p.His893Tyr Uncertain significance ★★ ⚠ same type
- ANKLE2 p.Lys473Arg Uncertain significance ★★ ⚠ same type
- ANKLE2 p.Phe549Val Uncertain significance ★★ ⚠ same type
- ANKLE2 p.Pro377Leu 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-ala688 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown