ANK1 p.Val575=
c.1725G>A · rs370616969 · VCV751131
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0347%, mid)
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 0.2 | GERP 1.1, phastCons 0.97 |
| Overall | ||
| CADD | 9.887 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0347%
Middle Eastern · 2/5,770 alleles
Filtering AF
0.00609%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00533%
Overall
0.00602%
93/1,545,054 alleles · ultra-rare
exomes 86/1,392,898 · genomes 7/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0347% | 2,885 |
| Remaining individualsnot grpmax-eligible | 0.0119% | 8,399 |
| European (non-Finnish) | 0.00703% | 14,219 |
| Admixed American | 0.00536% | 18,649 |
| African / African-American | 0.00136% | 73,572 |
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.Val575=
- Coding
- c.1725G>A
- MANE Select
- NM_000037
- dbSNP
- rs370616969
- Type
- single nucleotide variant
- Location
- chr8:41714231 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 575
- an α-helix; the '89 kda domain' region
Similar variants
- ANK1 p.Val575Leu 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-val575 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown