ANK1 c.4537+321T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 99.9%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +321 | deep intronic (+321 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.58 | GERP -1.8 |
| Overall | ||
| CADD | 0.092 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
99.9%
East Asian · 5,178/5,182 alleles
Filtering AF
97.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 96.7%
Overall
95.3%
145,158/152,330 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 99.9% | 1 |
| South Asian | 99.1% | 1 |
| Amishnot grpmax-eligible | 99.1% | 1 |
| Finnishnot grpmax-eligible | 97.3% | 1 |
| Admixed American | 97.2% | 1 |
| European (non-Finnish) | 96.6% | 1 |
| Remaining individualsnot grpmax-eligible | 95.7% | 1 |
| Middle Eastern | 95.6% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 93.1% | 1 |
| African / African-American | 91% | 1 |
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
- ANK1
- Coding
- c.4537+321T>C
- MANE Select
- NM_000037
- dbSNP
- rs572033
- Type
- single nucleotide variant
- Location
- chr8:41684223 (GRCh38)
- Gene constraint
- LOEUF 0.299 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 69.64 · 21 PDB
Similar variants
- ANK1 c.1305+1G>A Pathogenic ★★ same type
- ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same type
- ANK1 c.1801-2A>T Likely pathogenic ★★ same type
- ANK1 c.1998+1G>T Likely pathogenic ★★ same type
- ANK1 c.2296-1G>A Likely pathogenic ★★ same type
- ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ 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/ank1-c-4537-plus-321t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown