Is ATP7B p.Asp730= (c.2190C>T) pathogenic?

ATP7B p.Asp730= (c.2190C>T) is classified Conflicting classifications of pathogenicity in ATP7B (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0735%, eas); Associated with Wilson disease.

What condition is associated with ATP7B p.Asp730= (c.2190C>T)?

ATP7B p.Asp730= (c.2190C>T) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Asp730= (c.2190C>T) in the general population?

ATP7B p.Asp730= (c.2190C>T) is ultra-rare (popmax 0.0735%, eas) (gnomAD).

How is Wilson disease inherited?

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

ATP7B p.Asp730=

c.2190C>T · rs550565277 · VCV514917

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0735%, eas)

Conditions

Wilson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.553	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7	GERP -4
Overall
CADD	4.455	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0735% East Asian · 33/44,896 alleles

Filtering AF 0.0537% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.047%

Overall 0.00483% 78/1,614,232 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0735%	1,360
Middle Eastern	0.0165%	6,062
Admixed American	0.00666%	15,008
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	0.00305%	32,779
African / African-American	0.00133%	75,052

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.Asp730=
Coding: c.2190C>T
MANE Select: NM_000053
dbSNP: rs550565277
Type: single nucleotide variant
Location: chr13:51958476 (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 730: 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.Asp730Glu Uncertain significance ★ ⚠ same residue
ATP7B p.Asp730fs Pathogenic/Likely pathogenic ★★ 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-asp730 (accessed [today's date]).

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