ANK3 p.Ser1274=
c.3822C>G · rs184515022 · VCV722658
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.29%, amr)
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 1.9 | GERP 0.88, phastCons 1 |
| Overall | ||
| CADD | 6.435 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.29%
Admixed American · 173/59,728 alleles
Filtering AF
0.254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.241%
Overall
0.0649%
1,047/1,612,564 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.29% | 345 |
| Ashkenazi Jewishnot grpmax-eligible | 0.196% | 510 |
| Remaining individualsnot grpmax-eligible | 0.0817% | 1,224 |
| European (non-Finnish) | 0.0639% | 1,566 |
| Middle Eastern | 0.0165% | 6,060 |
| African / African-American | 0.0133% | 7,493 |
| Finnishnot grpmax-eligible | 0.00156% | 64,004 |
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.Ser1274=
- Coding
- c.3822C>G
- MANE Select
- NM_020987
- dbSNP
- rs184515022
- Type
- single nucleotide variant
- Location
- chr10:60085180 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Residue 1274
- the zu5 2 domain; the 'upa domain' region
Similar variants
- ANK3 p.Ser1274Tyr Uncertain significance ★★ same residue
- ANK3 p.Ser1274Phe Uncertain significance ★ same residue
- 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
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-ser1274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown