ANK2 p.Thr3457=
c.10371G>A · rs142908806 · VCV238566
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 13 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.28%, mid)
Conditions
3
Cardiovascular phenotype
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 -0.85 | GERP -5.4 |
| Overall | ||
| CADD | 0.518 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.28%
Middle Eastern · 138/6,062 alleles
Filtering AF
1.97%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.85%
Overall
0.211%
3,404/1,614,034 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 2.28% | 44 |
| Ashkenazi Jewishnot grpmax-eligible | 0.426% | 235 |
| Remaining individualsnot grpmax-eligible | 0.314% | 319 |
| Admixed American | 0.255% | 392 |
| European (non-Finnish) | 0.22% | 454 |
| Amishnot grpmax-eligible | 0.219% | 456 |
| Finnishnot grpmax-eligible | 0.144% | 696 |
| South Asian | 0.0648% | 1,544 |
| African / African-American | 0.052% | 1,924 |
| East Asian | 0.00223% | 44,856 |
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
- ANK2
- Protein
- p.Thr3457=
- Coding
- c.10371G>A
- MANE Select
- NM_001148
- dbSNP
- rs142908806
- Type
- single nucleotide variant
- Location
- chr4:113358989 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 3457
- the 'disordered' region
Similar variants
- ANK2 p.Thr3457Met Uncertain significance ★★ ⚠ same residue
- ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK2 p.Arg1088Ter Pathogenic ★★ same condition
- ANK2 p.Arg3113Ter Pathogenic ★★ same condition
- ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK2 p.Arg977Ter Pathogenic ★★ same condition
- ANK2 c.11032+11G>T Uncertain significance ★★ same condition
- ANK2 c.11611-3T>A 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-thr3457 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown