ANK2 p.Arg990=
c.2970A>C · rs35956627 · VCV190527
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, afr)
Conditions
2
long QT syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.034 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -2.1 | GERP -4.9 |
| Overall | ||
| CADD | 2.956 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
African / African-American · 805/75,056 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.987%
Overall
0.0549%
887/1,614,208 alleles · low-frequency
exomes 421/1,461,866 · genomes 466/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.07% | 93 |
| Remaining individualsnot grpmax-eligible | 0.0816% | 1,226 |
| Admixed American | 0.0333% | 3,001 |
| Middle Eastern | 0.0165% | 6,062 |
| South Asian | 0.00439% | 22,770 |
| European (non-Finnish) | 0.000508% | 196,674 |
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.Arg990=
- Coding
- c.2970A>C
- MANE Select
- NM_001148
- dbSNP
- rs35956627
- Type
- single nucleotide variant
- Location
- chr4:113330315 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 990
- a β-strand; the zu5 1 domain; the 'interaction with sptbn1' region
Similar variants
- ANK2 p.Arg990Gln Uncertain significance ★★ ⚠ same residue
- ANK2 p.Arg990Ter Conflicting classifications of pathogenicity ★ ⚠ same residue
- ANK2 p.Arg1007Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK2 p.Arg1088Ter Pathogenic ★★ same condition
- ANK2 p.Arg3113Ter Pathogenic ★★ same condition
- ANK2 c.11032+11G>T Uncertain significance ★★ same condition
- ANK2 c.11611-3T>A Uncertain significance ★★ same condition
- ANK2 c.1783-3C>T 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-arg990 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown