Is ATP7A p.Phe780= (c.2340C>T) pathogenic?

ATP7A p.Phe780= (c.2340C>T) is classified Likely benign in ATP7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). Very rare (popmax 0.00175%, afr); Associated with occipital horn syndrome.

What condition is associated with ATP7A p.Phe780= (c.2340C>T)?

ATP7A p.Phe780= (c.2340C>T) is associated with occipital horn syndrome, X-linked distal spinal muscular atrophy type 3, Menkes disease (ClinVar).

How common is ATP7A p.Phe780= (c.2340C>T) in the general population?

ATP7A p.Phe780= (c.2340C>T) is very rare (popmax 0.00175%, afr) (gnomAD).

How is Occipital horn syndrome inherited?

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

ATP7A p.Phe780=

c.2340C>T · rs2077838145 · VCV1487452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00175%, afr)

Conditions

occipital horn syndrome

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 2.7	GERP 1.1, phastCons 1
Overall
CADD	11.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% African / African-American · 1/57,008 alleles

Overall 0.000899% 1/111,203 alleles · very rare

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.Phe780=
Coding: c.2340C>T
MANE Select: NM_000052
dbSNP: rs2077838145
Type: single nucleotide variant
Location: chrX:78013046 (GRCh38)
Structure: AlphaFold pLDDT 73.59 · 22 PDB

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

Disease context

occipital horn syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked distal spinal muscular atrophy type 3 Menkes disease

For Occipital horn syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy, Neonatal

Similar variants

ATP7A p.Phe780Leu Uncertain significance ★ ⚠ same residue
ATP7A p.Phe780fs Uncertain significance same residue
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

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-phe780 (accessed [today's date]).

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