ANK1 p.Ile1869Arg
c.5606T>G · rs748263198 · VCV2439068
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.045%, sas)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.464 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.93 | unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic |
| Overall | ||
| CADD | 24.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.045%
South Asian · 41/91,060 alleles
Filtering AF
0.0341%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0302%
Overall
0.00285%
46/1,613,862 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.045% | 2,221 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,242 |
| Admixed American | 0.00167% | 60,004 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Ile1869Arg
- Coding
- c.5606T>G
- MANE Select
- NM_000037
- dbSNP
- rs748263198
- Type
- single nucleotide variant
- Location
- chr8:41661503 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 1869
- the '55 kda regulatory 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-ile1869arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown