Is ATP7B p.Met996Val (c.2986A>G) pathogenic?

ATP7B p.Met996Val (c.2986A>G) is classified Likely pathogenic in ATP7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-05). AlphaMissense: likely pathogenic (0.8854); Absent from gnomAD v4.1; Associated with Wilson disease.

What condition is associated with ATP7B p.Met996Val (c.2986A>G)?

ATP7B p.Met996Val (c.2986A>G) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Met996Val (c.2986A>G) in the general population?

ATP7B p.Met996Val (c.2986A>G) 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.Met996Val (c.2986A>G)?

AlphaMissense predicts likely pathogenic (score 0.8854) — an in-silico prediction, not a clinical call.

ATP7B p.Met996Val

c.2986A>G · rs2547646291 · VCV2093508

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Wilson disease

Computational evidence

Protein change
AlphaMissense	0.8854	likely pathogenic ✓ concordant with ClinVar
REVEL	0.929	moderately pathogenic-leaning
SaProt	LLR -12.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.92 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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.Met996Val
Coding: c.2986A>G
MANE Select: NM_000053
dbSNP: rs2547646291
Type: single nucleotide variant
Location: chr13:51946358 (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 996: 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.Met996Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP7B p.Met996fs 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-met996val (accessed [today's date]).

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