Is ATP7B p.Val1297= (c.3891C>T) pathogenic?

ATP7B p.Val1297= (c.3891C>T) is classified Benign/Likely benign in ATP7B (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Low-frequency (popmax 3.53%, afr); Associated with Wilson disease.

What condition is associated with ATP7B p.Val1297= (c.3891C>T)?

ATP7B p.Val1297= (c.3891C>T) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Val1297= (c.3891C>T) in the general population?

ATP7B p.Val1297= (c.3891C>T) is low-frequency (popmax 3.53%, afr) (gnomAD).

How is Wilson disease inherited?

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

ATP7B p.Val1297=

c.3891C>T · rs114771537 · VCV157954

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.53%, afr)

Conditions

Wilson disease

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 -7.6	GERP -4
Overall
CADD	0.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.53% African / African-American · 2,653/75,050 alleles

Filtering AF 3.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.38%

Overall 0.19% 3,071/1,614,064 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.53%	28
Remaining individualsnot grpmax-eligible	0.28%	357
Admixed American	0.223%	448
Middle Eastern	0.066%	1,516
East Asian	0.029%	3,452
South Asian	0.011%	9,109
European (non-Finnish)	0.00695%	14,391

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.Val1297=
Coding: c.3891C>T
MANE Select: NM_000053
dbSNP: rs114771537
Type: single nucleotide variant
Location: chr13:51937488 (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 1297: a UniProt-annotated variant site (in); a UniProt-annotated variant site (in wd); a β-strand

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.Val1297Ile 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-val1297 (accessed [today's date]).

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