ANK3 p.Ala1374=
c.4122C>T · rs12249658 · VCV776513
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 3.43%, afr)
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 0.44 | GERP -3.2, phastCons 0.97 |
| Overall | ||
| CADD | 6.324 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.43%
African / African-American · 2,563/74,800 alleles
Filtering AF
3.32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.27%
Overall
0.178%
2,871/1,610,116 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.43% | 29 |
| Remaining individualsnot grpmax-eligible | 0.216% | 462 |
| Admixed American | 0.205% | 488 |
| Middle Eastern | 0.132% | 756 |
| South Asian | 0.00777% | 12,875 |
| European (non-Finnish) | 0.00306% | 32,726 |
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.Ala1374=
- Coding
- c.4122C>T
- MANE Select
- NM_020987
- dbSNP
- rs12249658
- Type
- single nucleotide variant
- Location
- chr10:60083570 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Residue 1374
- the 'upa domain' region
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-ala1374 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown