Is ATP7A p.Ser596= (c.1788C>T) pathogenic?

ATP7A p.Ser596= (c.1788C>T) is classified Likely benign in ATP7A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0178%, eas); Associated with Menkes disease.

What condition is associated with ATP7A p.Ser596= (c.1788C>T)?

ATP7A p.Ser596= (c.1788C>T) is associated with Menkes disease, X-linked distal spinal muscular atrophy type 3, occipital horn syndrome (ClinVar).

How common is ATP7A p.Ser596= (c.1788C>T) in the general population?

ATP7A p.Ser596= (c.1788C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

How is Menkes disease inherited?

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

ATP7A p.Ser596=

c.1788C>T · rs368747913 · VCV511765

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Menkes disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -0.83, phastCons 1
Overall
CADD	4.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 6/33,770 alleles

Filtering AF 0.00766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.00166% 20/1,207,115 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,628
South Asian	0.00529%	18,904
Remaining individualsnot grpmax-eligible	0.0021%	47,534
European (non-Finnish)	0.00112%	89,327

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: ATP7A
Protein: p.Ser596=
Coding: c.1788C>T
MANE Select: NM_000052
dbSNP: rs368747913
Type: single nucleotide variant
Location: chrX:78009182 (GRCh38)
Structure: AlphaFold pLDDT 73.59 · 22 PDB
Residue 596: a β-strand; the hma 7 domain

Full ATP7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Menkes disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked distal spinal muscular atrophy type 3 occipital horn syndrome

For Menkes disease (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ATP7A c.1544-1G>A Pathogenic/Likely pathogenic ★★ same condition
ATP7A c.1544-2A>T Likely pathogenic ★★ same condition
ATP7A c.1870-1G>C Pathogenic ★★ same condition
ATP7A c.2172+5G>C Pathogenic/Likely pathogenic ★★ same condition
ATP7A c.2499-1G>A Pathogenic ★★ same condition
ATP7A c.4005+1G>T Pathogenic/Likely pathogenic ★★ same condition
ATP7A p.Ala1362Val Pathogenic/Likely pathogenic ★★ same condition
ATP7A p.Arg201Ter 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/atp7a-p-ser596 (accessed [today's date]).

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