Is ATP6AP2 p.Ala87Pro (c.259G>C) pathogenic?

ATP6AP2 p.Ala87Pro (c.259G>C) is classified Uncertain significance in ATP6AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-05). AlphaMissense: likely benign (0.0802); Absent from gnomAD v4.1; Associated with syndromic X-linked intellectual disability Hedera type.

What condition is associated with ATP6AP2 p.Ala87Pro (c.259G>C)?

ATP6AP2 p.Ala87Pro (c.259G>C) is associated with syndromic X-linked intellectual disability Hedera type (ClinVar).

How common is ATP6AP2 p.Ala87Pro (c.259G>C) in the general population?

ATP6AP2 p.Ala87Pro (c.259G>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.Ala87Pro (c.259G>C)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

ATP6AP2 p.Ala87Pro

c.259G>C · rs1926620037 · VCV1435119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Hedera type

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -4.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 25 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	18.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Ala87Pro
Coding: c.259G>C
MANE Select: NM_005765
dbSNP: rs1926620037
Type: single nucleotide variant
Location: chrX:40591324 (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.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
ATP6AP2 p.Gly16Glu 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-ala87pro (accessed [today's date]).

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