Is ATP6AP2 p.Ser115= (c.345C>T) pathogenic?

ATP6AP2 p.Ser115= (c.345C>T) is classified Pathogenic in ATP6AP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-08-15). Absent from gnomAD v4.1; Associated with X-linked parkinsonism-spasticity syndrome.

What condition is associated with ATP6AP2 p.Ser115= (c.345C>T)?

ATP6AP2 p.Ser115= (c.345C>T) is associated with X-linked parkinsonism-spasticity syndrome (ClinVar).

How common is ATP6AP2 p.Ser115= (c.345C>T) in the general population?

ATP6AP2 p.Ser115= (c.345C>T) is absent from gnomAD v4.1 (gnomAD).

How is X-linked parkinsonism-spasticity syndrome inherited?

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

ATP6AP2 p.Ser115=

c.345C>T · rs397518480 · VCV88756

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

X-linked parkinsonism-spasticity syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP 0.037, phastCons 0.013
Overall
CADD	8.153	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: ATP6AP2
Protein: p.Ser115=
Coding: c.345C>T
MANE Select: NM_005765
dbSNP: rs397518480
Type: single nucleotide variant
Location: chrX:40597293 (GRCh38)
Structure: AlphaFold pLDDT 79.27 · 10 PDB

Full ATP6AP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

X-linked parkinsonism-spasticity syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked parkinsonism-spasticity syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult

Similar variants

ATP6AP2 c.38-5T>C Benign/Likely benign ★★ same condition
ATP6AP2 p.Asp350= Benign/Likely benign ★★ same condition
ATP6AP2 p.Ala286= Conflicting classifications of pathogenicity ★ same condition
ATP6AP2 p.Val164Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
ATP6AP2 p.Asp107= Pathogenic ★★ same type
ATP6AP2 p.Ala259Thr Uncertain significance ★★ ⚠ same type
ATP6AP2 p.Arg155Cys Uncertain significance ★★ ⚠ same type
ATP6AP2 p.Arg199His Uncertain significance ★★ ⚠ same type

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/atp6ap2-p-ser115 (accessed [today's date]).

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