Is ATP7B p.Pro760fs (c.2279_2280del) pathogenic?

ATP7B p.Pro760fs (c.22792280del) is classified Likely pathogenic in ATP7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD; Associated with Wilson disease.

What condition is associated with ATP7B p.Pro760fs (c.2279_2280del)?

ATP7B p.Pro760fs (c.2279_2280del) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Pro760fs (c.2279_2280del) in the general population?

ATP7B p.Pro760fs (c.2279_2280del) is absent from gnomAD (gnomAD).

How is Wilson disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATP7B p.Pro760fs

c.2279_2280del · rs2547715234 · VCV3071276

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Wilson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -1.1, phastCons 0.52

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATP7B
Protein: p.Pro760fs
Coding: c.2279_2280del
MANE Select: NM_000053
dbSNP: rs2547715234
Type: Deletion
Location: chr13:51958386 (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 760: a UniProt-annotated variant site (in wd; decreased copper transport activity; increased atpase activity); an α-helix

Full ATP7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Wilson disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Wilson disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

ATP7B p.Pro760His Likely pathogenic ★ same residue
ATP7B p.Pro760Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP7B c.1700_1707+16del Likely pathogenic ★★ same condition
ATP7B c.1705_1707+10del Pathogenic ★★ same condition
ATP7B c.2866-2del Pathogenic/Likely pathogenic ★★ same condition
ATP7B c.3700del Pathogenic ★★ same condition
ATP7B c.3904-2del Pathogenic/Likely pathogenic ★★ same condition
ATP7B c.-436_-422del 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-pro760fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown