Is ATP7B p.Lys910= (c.2730G>A) pathogenic?

ATP7B p.Lys910= (c.2730G>A) is classified Conflicting classifications of pathogenicity in ATP7B (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-10-15). Rare (popmax 0.115%, afr); Associated with Wilson disease.

What condition is associated with ATP7B p.Lys910= (c.2730G>A)?

ATP7B p.Lys910= (c.2730G>A) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Lys910= (c.2730G>A) in the general population?

ATP7B p.Lys910= (c.2730G>A) is rare (popmax 0.115%, afr) (gnomAD).

How is Wilson disease inherited?

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

ATP7B p.Lys910=

c.2730G>A · rs80145681 · VCV991418

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, afr)

Conditions

Wilson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.31	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.29	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% African / African-American · 86/75,028 alleles

Filtering AF 0.095% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.00644% 104/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.115%	872
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Admixed American	0.00833%	12,005
European (non-Finnish)	0.000339%	295,007

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.Lys910=
Coding: c.2730G>A
MANE Select: NM_000053
dbSNP: rs80145681
Type: single nucleotide variant
Location: chr13:51950007 (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 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
ATP7B c.1708-1G>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-lys910 (accessed [today's date]).

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