ANKLE2 p.Ser662=
c.1986C>T · rs114132434 · VCV789056
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.45%, 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 1.4 | phastCons 0.81 |
| Overall | ||
| CADD | 1.086 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.45%
African / African-American · 1,832/74,814 alleles
Filtering AF
2.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.32%
Overall
0.127%
2,049/1,607,288 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.45% | 41 |
| Remaining individualsnot grpmax-eligible | 0.18% | 555 |
| Admixed American | 0.144% | 696 |
| Middle Eastern | 0.0166% | 6,026 |
| South Asian | 0.0066% | 15,160 |
| European (non-Finnish) | 0.00111% | 90,486 |
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.Ser662=
- Coding
- c.1986C>T
- MANE Select
- NM_015114
- dbSNP
- rs114132434
- Type
- single nucleotide variant
- Location
- chr12:132730176 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 662
- a modified residue (phosphoserine); 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-ser662 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown