Is ATP7B p.Ala718fs (c.2152delinsTCC) pathogenic?

ATP7B p.Ala718fs (c.2152delinsTCC) is classified Likely pathogenic in ATP7B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). Absent from gnomAD; Associated with Wilson disease.

What condition is associated with ATP7B p.Ala718fs (c.2152delinsTCC)?

ATP7B p.Ala718fs (c.2152delinsTCC) is associated with Wilson disease (ClinVar).

How common is ATP7B p.Ala718fs (c.2152delinsTCC) in the general population?

ATP7B p.Ala718fs (c.2152delinsTCC) is absent from gnomAD (gnomAD).

How is Wilson disease inherited?

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

ATP7B p.Ala718fs

c.2152delinsTCC · rs2547716328 · VCV2436103

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Wilson disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATP7B
Protein: p.Ala718fs
Coding: c.2152delinsTCC
MANE Select: NM_000053
dbSNP: rs2547716328
Type: Indel
Location: chr13:51958514 (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 718: 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.Ala718_Tyr719insTer Pathogenic ★★ same residue
ATP7B p.Ala718= Likely benign ★ same residue
ATP7B p.Ala718Pro Uncertain significance ⚠ same residue
ATP7B p.Cys431fs Pathogenic/Likely pathogenic ★★ same condition
ATP7B p.Glu122fs Pathogenic/Likely pathogenic ★★ same condition
ATP7B p.Glu150fs Pathogenic/Likely pathogenic ★★ same condition
ATP7B p.Thr1232_Gln1233delinsLeuValHisTer Pathogenic/Likely pathogenic ★★ same condition
ATP7B c.1286-191_1365delinsGAA 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-ala718fs (accessed [today's date]).

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