ANK1 c.2196+12C>A
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +12 | near-intronic (+12 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.86 | GERP 0.61, phastCons 0.051 |
| Non-coding constraint | Z 4.06 | 1 kb window · o/e 0.73 · regional · uncalibrated |
| Overall | ||
| CADD | 4.689 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,882 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.000496%
8/1,611,834 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,480 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,418 |
| European (non-Finnish) | 8.49e-05% | 1,178,114 |
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
- ANK1
- Coding
- c.2196+12C>A
- MANE Select
- NM_000037
- dbSNP
- rs1401721115
- Type
- single nucleotide variant
- Location
- chr8:41704362 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
Similar variants
- ANK1 c.1305+1G>A Pathogenic ★★ same type
- ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1801-2A>T Likely pathogenic ★★ same type
- ANK1 c.1998+1G>T Likely pathogenic ★★ same type
- ANK1 c.2296-1G>A Likely pathogenic ★★ same type
- ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ 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/ank1-c-2196-plus-12c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown