Is ATP7A p.Ser577= (c.1731C>T) pathogenic?

ATP7A p.Ser577= (c.1731C>T) is classified Likely benign in ATP7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Absent from gnomAD v4.1; Associated with X-linked distal spinal muscular atrophy type 3.

What condition is associated with ATP7A p.Ser577= (c.1731C>T)?

ATP7A p.Ser577= (c.1731C>T) is associated with X-linked distal spinal muscular atrophy type 3, occipital horn syndrome, Menkes disease (ClinVar).

How common is ATP7A p.Ser577= (c.1731C>T) in the general population?

ATP7A p.Ser577= (c.1731C>T) is absent from gnomAD v4.1 (gnomAD).

How is X-linked distal spinal muscular atrophy type 3 inherited?

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

ATP7A p.Ser577=

c.1731C>T · rs2149093501 · VCV1114541

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

X-linked distal spinal muscular atrophy type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor loss · deltas
Constraint at this position
Conservation	phyloP -0.74	GERP -3.6, phastCons 0.007
Overall
CADD	1.141	PHRED · no single calibrated threshold — expert panels disagree

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: ATP7A
Protein: p.Ser577=
Coding: c.1731C>T
MANE Select: NM_000052
dbSNP: rs2149093501
Type: single nucleotide variant
Location: chrX:78009125 (GRCh38)
Structure: AlphaFold pLDDT 73.59 · 22 PDB
Residue 577: a turn; the hma 7 domain

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

Disease context

X-linked distal spinal muscular atrophy type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: occipital horn syndrome Menkes disease

For X-linked distal spinal muscular atrophy type 3 (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

ATP7A p.Ser577Phe 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
ATP7A p.Ala1362Val 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-ser577 (accessed [today's date]).

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