ANK1 p.Lys128=
c.384G>A · rs758750884 · VCV363050
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0516%, sas)
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 0.42 | GERP -0.008, phastCons 0.99 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0516%
South Asian · 47/91,090 alleles
Filtering AF
0.0398%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0357%
Overall
0.00316%
51/1,614,100 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0516% | 1,938 |
| Admixed American | 0.00167% | 60,006 |
| European (non-Finnish) | 0.000254% | 393,346 |
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.Lys128=
- Coding
- c.384G>A
- MANE Select
- NM_000037
- dbSNP
- rs758750884
- Type
- single nucleotide variant
- Location
- chr8:41727292 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 128
- an α-helix; the '89 kda domain' region
Similar variants
- ANK1 p.Lys128fs Pathogenic ★★ 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-lys128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown