ANK1 p.Ser1646Ter
c.4937C>A · VCV3717842
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ANK1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 38 of 43 |
| Splicing | ||
| SpliceAI | Δ0.89 | donor gain · deltas |
| Pangolin | Δ0.73 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 54.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ANK1
- Protein
- p.Ser1646Ter
- Coding
- c.4937C>A
- MANE Select
- NM_000037
- Type
- single nucleotide variant
- Location
- chr8:41672513 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
- Residue 1646
- the '55 kda regulatory domain' region; the 'disordered' region
Disease context
ANK1-related disorder
Similar variants
- ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same condition
- ANK1 p.Arg1053Ter Pathogenic ★★ same condition
- ANK1 p.Arg1682Ter Pathogenic ★★ same condition
- ANK1 p.Arg281Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK1 p.Arg286Ter Pathogenic ★★ same condition
- ANK1 p.Trp1600Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK1 p.Tyr1750Ter Likely pathogenic ★★ same condition
- ANK1 p.Arg699Trp Uncertain significance ★★ ⚠ 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-ser1646ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown