ANKLE2 p.Ser730=
c.2190G>A · rs202225435 · VCV713427
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.195%, nfe)
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 -5.7 | |
| Overall | ||
| CADD | 0.038 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.195%
European (non-Finnish) · 2,306/1,179,922 alleles
Filtering AF
0.189%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.186%
Overall
0.155%
2,496/1,613,394 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.195% | 512 |
| Remaining individualsnot grpmax-eligible | 0.162% | 619 |
| South Asian | 0.0384% | 2,602 |
| African / African-American | 0.0347% | 2,884 |
| Admixed American | 0.0317% | 3,158 |
| Finnishnot grpmax-eligible | 0.0126% | 7,937 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
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.Ser730=
- Coding
- c.2190G>A
- MANE Select
- NM_015114
- dbSNP
- rs202225435
- Type
- single nucleotide variant
- Location
- chr12:132729972 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 730
- a UniProt-annotated variant site (in mcph16; uncertain significance)
Similar variants
- ANKLE2 p.Ser730Leu Likely benign ★ same residue
- 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
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-ser730 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown