Is ATP6AP2 p.Val124= (c.372T>G) pathogenic?

ATP6AP2 p.Val124= (c.372T>G) is classified Likely benign in ATP6AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-29). Very rare (popmax 0.00706%, sas); Associated with syndromic X-linked intellectual disability Hedera type.

What condition is associated with ATP6AP2 p.Val124= (c.372T>G)?

ATP6AP2 p.Val124= (c.372T>G) is associated with syndromic X-linked intellectual disability Hedera type (ClinVar).

How common is ATP6AP2 p.Val124= (c.372T>G) in the general population?

ATP6AP2 p.Val124= (c.372T>G) is very rare (popmax 0.00706%, sas) (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.

ATP6AP2 p.Val124=

c.372T>G · rs768335960 · VCV1666692

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00706%, sas)

Conditions

syndromic X-linked intellectual disability Hedera type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.16	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.59, phastCons 1
Overall
CADD	8.801	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00706% South Asian · 4/56,688 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.000367% 4/1,089,628 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.Val124=
Coding: c.372T>G
MANE Select: NM_005765
dbSNP: rs768335960
Type: single nucleotide variant
Location: chrX:40597320 (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-val124 (accessed [today's date]).

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