Is ATP7B p.Ser744= (c.2232T>C) pathogenic?

ATP7B p.Ser744= (c.2232T>C) is classified Likely benign in ATP7B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-16). Absent from gnomAD v4.1; Associated with Wilson disease.

What condition is associated with ATP7B p.Ser744= (c.2232T>C)?

ATP7B p.Ser744= (c.2232T>C) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Ser744= (c.2232T>C) in the general population?

ATP7B p.Ser744= (c.2232T>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.

ATP7B p.Ser744=

c.2232T>C · rs2547715584 · VCV3019516

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Wilson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.314	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.65	GERP -4
Overall
CADD	7.746	PHRED · no single calibrated threshold — expert panels disagree

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.Ser744=
Coding: c.2232T>C
MANE Select: NM_000053
dbSNP: rs2547715584
Type: single nucleotide variant
Location: chr13:51958434 (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 744: a UniProt-annotated variant site (in wd); 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.Ser744Pro Pathogenic/Likely pathogenic ★★ same residue
ATP7B p.Ser744Cys Uncertain significance ★ ⚠ same residue
ATP7B p.Ser744Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP7B p.Ser744Thr 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

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-ser744 (accessed [today's date]).

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