ATP2C2 p.Ala681=
c.2043C>T · rs374595905 · VCV3045079
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.143%, afr)
Conditions
1
ATP2C2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.42 | GERP -3.4, phastCons 0.99 |
| Overall | ||
| CADD | 8.168 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.143%
African / African-American · 107/74,900 alleles
Filtering AF
0.121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.113%
Overall
0.00923%
149/1,613,838 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.143% | 700 |
| Middle Eastern | 0.0493% | 2,027 |
| Admixed American | 0.0183% | 5,452 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,246 |
| South Asian | 0.00329% | 30,354 |
| European (non-Finnish) | 0.00127% | 78,663 |
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
- ATP2C2
- Protein
- p.Ala681=
- Coding
- c.2043C>T
- MANE Select
- NM_014861
- dbSNP
- rs374595905
- Type
- single nucleotide variant
- Location
- chr16:84454880 (GRCh38)
- Gene constraint
- LOEUF 1.712 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 81.13
Disease context
ATP2C2-related disorder
Similar variants
- ATP2C2 c.2580+1G>A Uncertain significance same condition
- ATP2C2 p.Ala223Asp Uncertain significance ⚠ same condition
- ATP2C2 c.1210-10C>T Likely benign same condition
- ATP2C2 c.1504-3A>G Likely benign same condition
- ATP2C2 c.1980+6C>T Likely benign same condition
- ATP2C2 c.2217-5C>T Likely benign same condition
- ATP2C2 c.2333+112T>A Likely benign same condition
- ATP2C2 c.2333+148A>G Likely benign 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/atp2c2-p-ala681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown