Is ATP6AP2 p.Pro36Ser (c.106C>T) pathogenic?

ATP6AP2 p.Pro36Ser (c.106C>T) is classified Uncertain significance in ATP6AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely benign (0.1614); Very rare (popmax 0.00525%, afr); Associated with syndromic X-linked intellectual disability Hedera type.

What condition is associated with ATP6AP2 p.Pro36Ser (c.106C>T)?

ATP6AP2 p.Pro36Ser (c.106C>T) is associated with syndromic X-linked intellectual disability Hedera type (ClinVar).

How common is ATP6AP2 p.Pro36Ser (c.106C>T) in the general population?

ATP6AP2 p.Pro36Ser (c.106C>T) is very rare (popmax 0.00525%, afr) (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.Pro36Ser (c.106C>T)?

AlphaMissense predicts likely benign (score 0.1614) — an in-silico prediction, not a clinical call.

ATP6AP2 p.Pro36Ser

c.106C>T · rs202105468 · VCV1462415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00525%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

syndromic X-linked intellectual disability Hedera type

Computational evidence

Protein change
AlphaMissense	0.1614	likely benign
REVEL	0.274	benign-leaning
SaProt	LLR -5.75	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	GERP 1.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 25 kb · p 3.4e-09 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00525% African / African-American · 3/57,120 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000686%

Overall 0.000249% 3/1,206,906 alleles · very rare

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: ATP6AP2
Protein: p.Pro36Ser
Coding: c.106C>T
MANE Select: NM_005765
dbSNP: rs202105468
Type: single nucleotide variant
Location: chrX:40589054 (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-pro36ser (accessed [today's date]).

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