Is ATP6AP2 p.Ser108= (c.324T>C) pathogenic?

ATP6AP2 p.Ser108= (c.324T>C) is classified Likely benign in ATP6AP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Very rare (popmax 0.000561%, nfe); Associated with syndromic X-linked intellectual disability Hedera type.

What condition is associated with ATP6AP2 p.Ser108= (c.324T>C)?

ATP6AP2 p.Ser108= (c.324T>C) is associated with syndromic X-linked intellectual disability Hedera type (ClinVar).

How common is ATP6AP2 p.Ser108= (c.324T>C) in the general population?

ATP6AP2 p.Ser108= (c.324T>C) is very rare (popmax 0.000561%, nfe) (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.Ser108=

c.324T>C · rs772002758 · VCV1608405

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000561%, nfe)

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	0.227	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.4	GERP -3.8
Overall
CADD	2.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000561% European (non-Finnish) · 5/891,214 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000415% 5/1,206,062 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.Ser108=
Coding: c.324T>C
MANE Select: NM_005765
dbSNP: rs772002758
Type: single nucleotide variant
Location: chrX:40597272 (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.Ser108Asn 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-ser108 (accessed [today's date]).

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