Is ATP6AP2 p.Ala128Pro (c.382G>C) pathogenic?

ATP6AP2 p.Ala128Pro (c.382G>C) is classified Uncertain significance in ATP6AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely pathogenic (0.9517); Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability Hedera type.

What condition is associated with ATP6AP2 p.Ala128Pro (c.382G>C)?

ATP6AP2 p.Ala128Pro (c.382G>C) is associated with syndromic X-linked intellectual disability Hedera type (ClinVar).

How common is ATP6AP2 p.Ala128Pro (c.382G>C) in the general population?

ATP6AP2 p.Ala128Pro (c.382G>C) is absent from gnomAD v4.1 (gnomAD).

How is X-linked intellectual disability, Hedera type inherited?

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

What do computational predictors say about ATP6AP2 p.Ala128Pro (c.382G>C)?

AlphaMissense predicts likely pathogenic (score 0.9517) — an in-silico prediction, not a clinical call.

ATP6AP2 p.Ala128Pro

c.382G>C · VCV3701673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9517 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Hedera type

Computational evidence

Protein change
AlphaMissense	0.9517	likely pathogenic · top 10% in ATP6AP2
REVEL	0.232	benign-leaning
SaProt	LLR -10.12	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.99, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 25 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Ala128Pro
Coding: c.382G>C
MANE Select: NM_005765
Type: single nucleotide variant
Location: chrX:40597330 (GRCh38)
Structure: AlphaFold pLDDT 79.27 · 10 PDB

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

Disease context

syndromic X-linked intellectual disability Hedera type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked intellectual disability, Hedera type (Orphanet):

Inheritance: X-linked recessive
Onset: Infancy

Similar variants

ATP6AP2 p.Ala128Val Uncertain significance ★ ⚠ same residue
ATP6AP2 p.Asp107= Pathogenic ★★ same condition
ATP6AP2 p.Ala259Thr Uncertain significance ★★ ⚠ same condition
ATP6AP2 p.Arg155Cys Uncertain significance ★★ ⚠ same condition
ATP6AP2 p.Arg199His Uncertain significance ★★ ⚠ same condition
ATP6AP2 p.Arg41Gln Uncertain significance ★★ ⚠ same condition
ATP6AP2 p.Asn17Ser Uncertain significance ★★ ⚠ same condition
ATP6AP2 p.Asp242Asn Uncertain significance ★★ ⚠ 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/atp6ap2-p-ala128pro (accessed [today's date]).

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