ANK1 p.Arg1377del
c.4125_4127del · VCV4700115
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0187%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.83 | GERP -4.3, phastCons 0.009 |
| Overall | ||
| CADD | 11.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0187%
South Asian · 17/91,070 alleles
Filtering AF
0.0118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00976%
Overall
0.00105%
17/1,614,014 alleles · ultra-rare
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.Arg1377del
- Coding
- c.4125_4127del
- MANE Select
- NM_000037
- Type
- Deletion
- Location
- chr8:41688567 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
Similar variants
- ANK1 p.Arg1377fs Pathogenic/Likely pathogenic ★★ same residue
- ANK1 p.Ala1605fs Likely pathogenic ★★ same type
- ANK1 p.Ala461fs Likely pathogenic ★★ same type
- ANK1 p.Ala983fs Pathogenic ★★ same type
- ANK1 p.Arg1137fs Pathogenic/Likely pathogenic ★★ same type
- ANK1 p.Asn756fs Likely pathogenic ★★ same type
- ANK1 p.Cys1216_Pro1217insTer Pathogenic/Likely pathogenic ★★ same type
- ANK1 p.Gln471fs 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-arg1377del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown