ANK1 p.Pro440=
c.1320G>A · rs28533718 · VCV261289
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 9.14%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
2
Spherocytosis
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 -7.1 | GERP -4.3 |
| Overall | ||
| CADD | 5.111 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9.14%
African / African-American · 6,857/75,036 alleles
Filtering AF
8.96%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 8.88%
Overall
1.76%
28,350/1,614,124 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 9.14% | 11 |
| Amishnot grpmax-eligible | 4.17% | 24 |
| Ashkenazi Jewishnot grpmax-eligible | 3% | 33 |
| South Asian | 2.88% | 35 |
| Remaining individualsnot grpmax-eligible | 1.85% | 54 |
| Middle Eastern | 1.67% | 60 |
| Finnishnot grpmax-eligible | 1.29% | 78 |
| European (non-Finnish) | 1.28% | 78 |
| Admixed American | 1.23% | 82 |
| East Asian | 0.0201% | 4,987 |
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.Pro440=
- Coding
- c.1320G>A
- MANE Select
- NM_000037
- dbSNP
- rs28533718
- Type
- single nucleotide variant
- Location
- chr8:41717037 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 440
- an α-helix; the '89 kda domain' region
Similar variants
- ANK1 p.Pro440Leu Uncertain significance ★★ ⚠ same residue
- ANK1 c.1305+1G>A Pathogenic ★★ same condition
- ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same condition
- ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same condition
- ANK1 c.2296-1G>A Likely pathogenic ★★ same condition
- ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ANK1 c.2389-2A>G Likely pathogenic ★★ same condition
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-pro440 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown