ANK1 p.Ala447=
c.1341C>T · rs768336827 · VCV741619
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0366%, amr)
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 -0.45 | GERP -4.3, phastCons 0.093 |
| Overall | ||
| CADD | 11.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0366%
Admixed American · 22/60,036 alleles
Filtering AF
0.0248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0209%
Overall
0.00285%
46/1,614,230 alleles · ultra-rare
exomes 34/1,461,888 · genomes 12/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0366% | 2,729 |
| East Asian | 0.0111% | 8,978 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| African / African-American | 0.00133% | 75,064 |
| South Asian | 0.0011% | 91,076 |
| European (non-Finnish) | 0.00102% | 98,336 |
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
- Protein
- p.Ala447=
- Coding
- c.1341C>T
- MANE Select
- NM_000037
- dbSNP
- rs768336827
- Type
- single nucleotide variant
- Location
- chr8:41717016 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 447
- an α-helix; the '89 kda domain' region
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-p-ala447 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown