Is ATP7B p.Arg919Trp (c.2755C>T) pathogenic?

ATP7B p.Arg919Trp (c.2755C>T) is classified Pathogenic/Likely pathogenic in ATP7B (ClinVar, Multiple submitters, 20 submitters; last evaluated 2026-08-03). AlphaMissense: likely benign (0.2446); Ultra-rare (popmax 0.0121%, sas); Associated with ATP7B-related disorder.

What condition is associated with ATP7B p.Arg919Trp (c.2755C>T)?

ATP7B p.Arg919Trp (c.2755C>T) is associated with ATP7B-related disorder, Wilson disease (ClinVar).

How common is ATP7B p.Arg919Trp (c.2755C>T) in the general population?

ATP7B p.Arg919Trp (c.2755C>T) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about ATP7B p.Arg919Trp (c.2755C>T)?

AlphaMissense predicts likely benign (score 0.2446) — an in-silico prediction, not a clinical call.

ATP7B p.Arg919Trp

c.2755C>T · rs121907993 · VCV312386

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 20 submitters

AlphaMissense

likely benign

0.2446 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ATP7B-related disorder

Computational evidence

Protein change
AlphaMissense	0.2446	likely benign ⚠ discordant with ClinVar
REVEL	0.75	pathogenic-leaning
SaProt	LLR -10.82	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.92 · regional, not allelic
Overall
CADD	27.1	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

Grpmax group 0.0121% South Asian · 11/91,072 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00322% 52/1,613,962 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,279
African / African-American	0.00933%	10,716
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00446%	22,439
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,010
European (non-Finnish)	0.00203%	49,167
Finnishnot grpmax-eligible	0.00157%	63,890

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.Arg919Trp
Coding: c.2755C>T
MANE Select: NM_000053
dbSNP: rs121907993
Type: single nucleotide variant
Location: chr13:51949772 (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 919: 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

ATP7B-related disorder

Also linked: Wilson disease

Similar variants

ATP7B p.Arg919Gln Uncertain significance ★★ ⚠ same residue
ATP7B p.Arg919Leu Likely pathogenic ★ ⚠ same residue
ATP7B p.Arg919Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP7B p.Arg919= Likely benign ★ same residue
ATP7B p.Arg919fs 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

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-arg919trp (accessed [today's date]).

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