ATP7B p.Ala756=
c.2268G>A · rs755387536 · VCV254763
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, amr)
Conditions
2
Inborn genetic diseases
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 -13 | GERP -4 |
| Overall | ||
| CADD | 0.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
Admixed American · 4/60,004 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000929%
15/1,614,086 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00667% | 15,001 |
| South Asian | 0.00329% | 30,362 |
| East Asian | 0.00223% | 44,900 |
| European (non-Finnish) | 0.000593% | 168,578 |
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
- ATP7B
- Protein
- p.Ala756=
- Coding
- c.2268G>A
- MANE Select
- NM_000053
- dbSNP
- rs755387536
- Type
- single nucleotide variant
- Location
- chr13:51958398 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 71.83 · 13 PDB
- Residue 756
- a UniProt-annotated variant site (in wd)
Similar variants
- ATP7B p.Ala756Val Conflicting classifications of pathogenicity ★ ⚠ same residue
- ATP7B c.1285+2T>A Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1286-2A>G Pathogenic ★★ same condition
- ATP7B c.1543+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1543+1G>C Pathogenic ★★ same condition
- ATP7B c.1544-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1707+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ATP7B c.1707+5G>A Pathogenic ★★ 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/atp7b-p-ala756 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown