ATP8A2 c.1663-20G>A
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00434%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | acceptor -20 | acceptor splice region (-20, within the last 20 intronic nt) · inside the BP7-excluded zone |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.34 | GERP -3.5 |
| Non-coding constraint | Z 0.23 | 1 kb window · o/e 0.98 · regional · uncalibrated |
| Overall | ||
| CADD | 4.569 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00434%
European (non-Finnish) · 46/1,058,822 alleles
Filtering AF
0.00333%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00298%
Overall
0.00318%
47/1,479,552 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00434% | 23,018 |
| African / African-American | 0.00139% | 71,938 |
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
- ATP8A2
- Coding
- c.1663-20G>A
- MANE Select
- NM_016529
- dbSNP
- rs374448080
- Type
- single nucleotide variant
- Location
- chr13:25574788 (GRCh38)
- Gene constraint
- LOEUF 0.728 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 81.12
Similar variants
- ATP8A2 c.1782+2T>C Pathogenic ★★ same type
- ATP8A2 c.2212-1G>C Pathogenic ★★ same type
- ATP8A2 c.3272+1G>A Pathogenic/Likely pathogenic ★★ same type
- ATP8A2 c.77-2A>G Pathogenic/Likely pathogenic ★★ same type
- ATP8A2 p.Arg586Ter Pathogenic/Likely pathogenic ★★ same type
- ATP8A2 p.Asp765Tyr Likely pathogenic ★★ same type
- ATP8A2 p.Ala1091Val Uncertain significance ★★ ⚠ same type
- ATP8A2 p.Ala335Thr Uncertain significance ★★ ⚠ 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/atp8a2-c-1663-minus-20g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown