ATP8A2 p.Ala554=
c.1662G>A · rs765757067 · VCV1909334
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.48 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.7 |
| Overall | ||
| CADD | 11.24 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,002 alleles
Filtering AF
0.000764%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000606%
Overall
0.00112%
18/1,613,310 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,002 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,458 |
| African / African-American | 0.00133% | 74,908 |
| European (non-Finnish) | 0.00127% | 78,624 |
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
- Protein
- p.Ala554=
- Coding
- c.1662G>A
- MANE Select
- NM_016529
- dbSNP
- rs765757067
- Type
- single nucleotide variant
- Location
- chr13:25571692 (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 p.Ala554Gly Uncertain significance ★ ⚠ same residue
- 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
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-p-ala554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown