ANK1 p.Ser594=
c.1782C>A · rs61753679 · VCV261294
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.92%, nfe)
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 1 | GERP 0.086, phastCons 1 |
| Overall | ||
| CADD | 8.963 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.92%
European (non-Finnish) · 42,351/1,081,444 alleles
Filtering AF
3.88%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.87%
Overall
3.26%
47,038/1,443,150 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 3.92% | 26 |
| Remaining individualsnot grpmax-eligible | 2.93% | 34 |
| Admixed American | 2.47% | 40 |
| Amishnot grpmax-eligible | 2.09% | 48 |
| Finnishnot grpmax-eligible | 1.53% | 66 |
| Ashkenazi Jewishnot grpmax-eligible | 0.972% | 103 |
| African / African-American | 0.619% | 161 |
| South Asian | 0.507% | 197 |
| Middle Eastern | 0.376% | 266 |
| East Asian | 0.0122% | 8,226 |
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.Ser594=
- Coding
- c.1782C>A
- MANE Select
- NM_000037
- dbSNP
- rs61753679
- Type
- single nucleotide variant
- Location
- chr8:41714174 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 594
- the '89 kda domain' region
Similar variants
- 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
- ANK1 c.2462-2A>G 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-ser594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown