ANKLE2 p.His552=
c.1656C>T · rs774535092 · VCV742806
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.34 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.1 | |
| Overall | ||
| CADD | 0.211 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,084 alleles
Filtering AF
0.00157%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00134%
Overall
0.00204%
33/1,613,958 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,361 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| European (non-Finnish) | 0.00229% | 43,705 |
| East Asian | 0.00223% | 44,898 |
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.His552=
- Coding
- c.1656C>T
- MANE Select
- NM_015114
- dbSNP
- rs774535092
- Type
- single nucleotide variant
- Location
- chr12:132735450 (GRCh38)
- Gene constraint
- LOEUF 0.825 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.14
- Residue 552
- a UniProt-annotated variant site (in mcph16; uncertain significance)
Similar variants
- ANKLE2 p.His552Gln Uncertain significance ★ ⚠ 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-his552 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown