ANK2 c.3379+4C>A
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00254%, nfe)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +4 | donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.38 | GERP 0.43, phastCons 0.1 |
| Non-coding constraint | Z 2.78 | 1 kb window · o/e 0.80 · regional · uncalibrated |
| Overall | ||
| CADD | 8.336 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00254%
European (non-Finnish) · 30/1,180,024 alleles
Filtering AF
0.0018%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00156%
Overall
0.00198%
32/1,613,908 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00254% | 39,334 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,488 |
| African / African-American | 0.00134% | 74,854 |
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
- Coding
- c.3379+4C>A
- MANE Select
- NM_001148
- dbSNP
- rs752152002
- Type
- single nucleotide variant
- Location
- chr4:113333212 (GRCh38)
- Gene constraint
- LOEUF 0.271 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- ANK2 p.Arg3113Ter Pathogenic ★★ same condition
- ANK2 p.Arg895Ter Pathogenic/Likely pathogenic ★★ same condition
- ANK2 p.Arg977Ter Pathogenic ★★ 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
- ANK2 c.3125+6G>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-c-3379-plus-4c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown