ANK3 p.Pro1323=
c.3969C>T · rs140104995 · VCV1298485
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, 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 -1.2 | GERP -9.5 |
| Overall | ||
| CADD | 8.288 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
African / African-American · 35/75,008 alleles
Filtering AF
0.0345%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0302%
Overall
0.00954%
154/1,613,648 alleles · ultra-rare
exomes 128/1,461,472 · genomes 26/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0467% | 2,143 |
| Finnishnot grpmax-eligible | 0.0328% | 3,047 |
| Remaining individualsnot grpmax-eligible | 0.0272% | 3,676 |
| Middle Eastern | 0.0165% | 6,056 |
| Admixed American | 0.0117% | 8,556 |
| European (non-Finnish) | 0.00585% | 17,099 |
| East Asian | 0.00446% | 22,427 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| South Asian | 0.0011% | 91,022 |
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.Pro1323=
- Coding
- c.3969C>T
- MANE Select
- NM_020987
- dbSNP
- rs140104995
- Type
- single nucleotide variant
- Location
- chr10:60084707 (GRCh38)
- Gene constraint
- LOEUF 0.16 · pLI 1.00 (gnomAD)
- Residue 1323
- the 'upa domain' region
Similar variants
- ANK3 p.Pro1323Ser Uncertain significance ★★ ⚠ same residue
- ANK3 p.Pro1323Ala 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-pro1323 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown