ANK1 p.Pro1858=
c.5574G>A · rs139528300 · VCV739022
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0274%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| REVEL | 0.223 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | Δ0.20 | acceptor loss · deltas |
| Constraint at this position | ||
| Conservation | phyloP -0.27 | GERP -4.2, phastCons 0.038 |
| Overall | ||
| CADD | 17.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0274%
South Asian · 25/91,076 alleles
Filtering AF
0.019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0163%
Overall
0.00347%
56/1,614,004 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0274% | 3,643 |
| African / African-American | 0.016% | 6,253 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,252 |
| Admixed American | 0.00167% | 60,018 |
| European (non-Finnish) | 0.00136% | 73,752 |
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.Pro1858=
- Coding
- c.5574G>A
- MANE Select
- NM_000037
- dbSNP
- rs139528300
- Type
- single nucleotide variant
- Location
- chr8:41661535 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 1858
- the '55 kda regulatory domain' region; the 'disordered' region
Similar variants
- ANK1 p.Pro1858Leu Uncertain significance ★ same residue
- 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
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-pro1858 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown