ATP8A2 p.Leu247=
c.741C>T · VCV4749987
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00271%, nfe)
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 -0.69 | GERP -3.2, phastCons 0.008 |
| Overall | ||
| CADD | 7.446 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
European (non-Finnish) · 32/1,179,968 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00211%
34/1,613,928 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00271% | 36,874 |
| Admixed American | 0.00167% | 59,998 |
| African / African-American | 0.00134% | 74,884 |
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.Leu247=
- Coding
- c.741C>T
- MANE Select
- NM_016529
- Type
- single nucleotide variant
- Location
- chr13:25542008 (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.Leu247Phe 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-leu247 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown