ANK2 p.Glu3590Ter
c.10768G>T · rs2506612939 · VCV3068471
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
ANK2-associated Neurodevelopmental Disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 40 of 46 |
| REVEL | 0.774 | moderately pathogenic-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 51.0 | 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
- ANK2
- Protein
- p.Glu3590Ter
- Coding
- c.10768G>T
- MANE Select
- NM_001148
- dbSNP
- rs2506612939
- Type
- single nucleotide variant
- Location
- chr4:113363349 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 3590
- an α-helix; the death 2 domain
Disease context
ANK2-associated Neurodevelopmental Disorder
Similar variants
- ANK2 p.Glu3590= Likely benign ★★ same residue
- ANK2 p.Arg1088Ter Pathogenic ★★ same condition
- ANK2 p.Arg888Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK2 c.85-28508A>G Uncertain significance ★★ same condition
- ANK2 c.85-57022A>C Uncertain significance ★★ same condition
- ANK2 p.Ala41Thr Uncertain significance ★★ ⚠ same condition
- ANK2 p.Gln2672His Uncertain significance ★★ ⚠ same condition
- ANK2 p.Lys114Glu 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/ank2-p-glu3590ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown