ATP2A2 p.Ala581=
c.1743C>A · VCV3625301
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00934%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.222 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 12.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00934%
African / African-American · 7/74,910 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000558%
9/1,613,876 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00934% | 10,701 |
| Admixed American | 0.00167% | 60,002 |
| South Asian | 0.0011% | 91,078 |
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
- ATP2A2
- Protein
- p.Ala581=
- Coding
- c.1743C>A
- MANE Select
- NM_170665
- Type
- single nucleotide variant
- Location
- chr12:110339703 (GRCh38)
- Gene constraint
- LOEUF 0.205 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.46 · 15 PDB
- Residue 581
- an α-helix; the 'interaction with hax1' region
Similar variants
- ATP2A2 p.Ala803Thr Pathogenic/Likely pathogenic ★★ same type
- ATP2A2 p.Asn767Ser Pathogenic/Likely pathogenic ★★ same type
- ATP2A2 p.Asp702Asn Pathogenic ★★ same type
- ATP2A2 p.Gly211Asp Pathogenic ★★ same type
- ATP2A2 p.Ile348Thr Pathogenic/Likely pathogenic ★★ same type
- ATP2A2 p.Met1Leu Pathogenic ★★ same type
- ATP2A2 p.Met1Val Pathogenic ★★ same type
- ATP2A2 p.Pro602Leu 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/atp2a2-p-ala581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown