Is ATP7B p.Gln4Pro (c.11A>C) pathogenic?

ATP7B p.Gln4Pro (c.11A>C) is classified Uncertain significance in ATP7B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-03). AlphaMissense: likely benign (0.0606); Absent from gnomAD v4.1; Associated with Wilson disease.

What condition is associated with ATP7B p.Gln4Pro (c.11A>C)?

ATP7B p.Gln4Pro (c.11A>C) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Gln4Pro (c.11A>C) in the general population?

ATP7B p.Gln4Pro (c.11A>C) is absent from gnomAD v4.1 (gnomAD).

How is Wilson disease inherited?

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

What do computational predictors say about ATP7B p.Gln4Pro (c.11A>C)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

ATP7B p.Gln4Pro

c.11A>C · rs781780227 · VCV984509

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wilson disease

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -3.2
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.92 · regional, not allelic
Overall
CADD	4.908	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATP7B
Protein: p.Gln4Pro
Coding: c.11A>C
MANE Select: NM_000053
dbSNP: rs781780227
Type: single nucleotide variant
Location: chr13:52011327 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 13 PDB

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.Gln4Glu Uncertain significance ★★ ⚠ same residue
ATP7B p.Gln4Leu Uncertain significance ★ ⚠ 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

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-gln4pro (accessed [today's date]).

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