Is ATP7A p.Val751= (c.2253G>A) pathogenic?

ATP7A p.Val751= (c.2253G>A) is classified Likely benign in ATP7A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). Very rare (popmax 0.00526%, sas); Associated with X-linked distal spinal muscular atrophy type 3.

What condition is associated with ATP7A p.Val751= (c.2253G>A)?

ATP7A p.Val751= (c.2253G>A) is associated with X-linked distal spinal muscular atrophy type 3, occipital horn syndrome, Menkes disease (ClinVar).

How common is ATP7A p.Val751= (c.2253G>A) in the general population?

ATP7A p.Val751= (c.2253G>A) is very rare (popmax 0.00526%, sas) (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.Val751=

c.2253G>A · rs782375469 · VCV1623779

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00526%, sas)

Conditions

X-linked distal spinal muscular atrophy type 3

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 0.37	GERP -1.6, phastCons 0.14
Overall
CADD	6.265	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00526% South Asian · 3/56,985 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000856%

Overall 0.00157% 19/1,211,525 alleles · very rare exomes 19/1,097,965 · genomes 0/113,560 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00526%	18,995
European (non-Finnish)	0.00179%	55,959

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.Val751=
Coding: c.2253G>A
MANE Select: NM_000052
dbSNP: rs782375469
Type: single nucleotide variant
Location: chrX:78012959 (GRCh38)
Structure: AlphaFold pLDDT 73.59 · 22 PDB

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.Val751Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ATP7A p.Val751fs Pathogenic ★ 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-val751 (accessed [today's date]).

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