Is ATP6AP1 p.Ser129Pro (c.385T>C) pathogenic?

ATP6AP1 p.Ser129Pro (c.385T>C) is classified Uncertain significance in ATP6AP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). AlphaMissense: likely pathogenic (0.8305); Absent from gnomAD v4.1; Associated with immunodeficiency 47.

What condition is associated with ATP6AP1 p.Ser129Pro (c.385T>C)?

ATP6AP1 p.Ser129Pro (c.385T>C) is associated with immunodeficiency 47 (ClinVar).

How common is ATP6AP1 p.Ser129Pro (c.385T>C) in the general population?

ATP6AP1 p.Ser129Pro (c.385T>C) is absent from gnomAD v4.1 (gnomAD).

How is ATP6AP1-CDG inherited?

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

What do computational predictors say about ATP6AP1 p.Ser129Pro (c.385T>C)?

AlphaMissense predicts likely pathogenic (score 0.8305) — an in-silico prediction, not a clinical call.

ATP6AP1 p.Ser129Pro

c.385T>C · rs2523017472 · VCV2444113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8305 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 47

Computational evidence

Protein change
AlphaMissense	0.8305	likely pathogenic
REVEL	0.651	pathogenic-leaning
SaProt	LLR -14.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 3,718 bp · p 0.8 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: ATP6AP1
Protein: p.Ser129Pro
Coding: c.385T>C
MANE Select: NM_001183
dbSNP: rs2523017472
Type: single nucleotide variant
Location: chrX:154432287 (GRCh38)
Structure: AlphaFold pLDDT 79.60 · 9 PDB

Full ATP6AP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ATP6AP1-CDG (Orphanet):

Inheritance: X-linked recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ATP6AP1 p.Glu346Lys Pathogenic/Likely pathogenic ★★ same condition
ATP6AP1 p.Arg225His Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.Arg344His Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.Arg9Ter Uncertain significance ★★ same condition
ATP6AP1 p.Ser172Thr Uncertain significance ★★ ⚠ same condition
ATP6AP1 c.289-135= Benign ★★ same condition
ATP6AP1 p.Arg180His Benign/Likely benign ★★ same condition
ATP6AP1 p.Thr388Pro Benign/Likely benign ★★ 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/atp6ap1-p-ser129pro (accessed [today's date]).

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