ANKLE2 p.Asn656=
c.1968T>C · rs11545751 · VCV1257793
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 11.4%, 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 0.46 | phastCons 0.004 |
| Overall | ||
| CADD | 1.501 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.4%
African / African-American · 8,481/74,296 alleles
Filtering AF
11.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11.1%
Overall
0.67%
10,723/1,600,184 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 11.4% | 9 |
| Middle Eastern | 1.42% | 70 |
| Ashkenazi Jewishnot grpmax-eligible | 1.19% | 84 |
| Remaining individualsnot grpmax-eligible | 1.01% | 99 |
| Admixed American | 0.919% | 109 |
| European (non-Finnish) | 0.0523% | 1,911 |
| South Asian | 0.0508% | 1,969 |
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.Asn656=
- Coding
- c.1968T>C
- MANE Select
- NM_015114
- dbSNP
- rs11545751
- Type
- single nucleotide variant
- Location
- chr12:132730194 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 656
- 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-asn656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown