ANK3 p.Asp4165=
c.12495T>C · rs374346074 · VCV2081745
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00672%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.3 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 3, phastCons 1 |
| Overall | ||
| CADD | 6.645 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00672%
Admixed American · 4/59,490 alleles
Filtering AF
0.00342%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0031%
Overall
0.00366%
59/1,610,832 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00672% | 14,872 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,791 |
| European (non-Finnish) | 0.00441% | 22,675 |
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
- ANK3
- Protein
- p.Asp4165=
- Coding
- c.12495T>C
- MANE Select
- NM_020987
- dbSNP
- rs374346074
- Type
- single nucleotide variant
- Location
- chr10:60063211 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Residue 4165
- an α-helix; the death domain
Similar variants
- ANK3 c.2382+6C>T Uncertain significance ★★ same type
- ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
- ANK3 p.Ala1534Val Uncertain significance ★★ same type
- ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
- ANK3 p.Ala169Thr Uncertain significance ★★ same type
- ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
- ANK3 p.Ala218Thr Uncertain significance ★★ same type
- ANK3 p.Ala2223Thr Uncertain significance ★★ ⚠ 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/ank3-p-asp4165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown