ANK2 p.His271=
c.813T>C · rs774848857 · VCV519081
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.125%, eas)
Conditions
2
long QT syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.78 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -4.9 |
| Overall | ||
| CADD | 4.562 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.125%
East Asian · 56/44,876 alleles
Filtering AF
0.0986%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0892%
Overall
0.00613%
99/1,613,848 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.125% | 801 |
| Remaining individualsnot grpmax-eligible | 0.0624% | 1,602 |
| Admixed American | 0.00333% | 29,989 |
| Finnishnot grpmax-eligible | 0.00156% | 64,028 |
| European (non-Finnish) | 8.48e-05% | 1,179,903 |
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.His271=
- Coding
- c.813T>C
- MANE Select
- NM_001148
- dbSNP
- rs774848857
- Type
- single nucleotide variant
- Location
- chr4:113242131 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 271
- an α-helix
Similar variants
- 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
- ANK2 c.2079+5T>G Uncertain significance ★★ same condition
- ANK2 c.2278-3C>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-his271 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown