Is MAOA p.Arg454= (c.1360C>A) pathogenic?

MAOA p.Arg454= (c.1360C>A) is classified Likely benign in MAOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). Absent from gnomAD v4.1; Associated with Brunner syndrome.

What condition is associated with MAOA p.Arg454= (c.1360C>A)?

MAOA p.Arg454= (c.1360C>A) is associated with Brunner syndrome (ClinVar).

How common is MAOA p.Arg454= (c.1360C>A) in the general population?

MAOA p.Arg454= (c.1360C>A) is absent from gnomAD v4.1 (gnomAD).

How is Monoamine oxidase A deficiency inherited?

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

MAOA p.Arg454=

c.1360C>A · VCV3687160

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Brunner syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -0.26, phastCons 0.33
Overall
CADD	7.156	PHRED · no single calibrated threshold — expert panels disagree

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: MAOA
Protein: p.Arg454=
Coding: c.1360C>A
MANE Select: NM_000240
Type: single nucleotide variant
Location: chrX:43743891 (GRCh38)
Structure: AlphaFold pLDDT 97.09 · 4 PDB
Residue 454: an α-helix

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

Disease context

Brunner syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Monoamine oxidase A deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

MAOA p.Arg454Gln Uncertain significance ★ ⚠ same residue
MAOA p.Arg45Trp Pathogenic/Likely pathogenic ★★ same condition
MAOA c.796-10T>C Uncertain significance ★★ same condition
MAOA p.Ala111Thr Uncertain significance ★★ ⚠ same condition
MAOA p.Arg109Trp Uncertain significance ★★ ⚠ same condition
MAOA p.Arg45Gln Uncertain significance ★★ ⚠ same condition
MAOA p.Asn125Ser Uncertain significance ★★ ⚠ same condition
MAOA p.Asp46Gly 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/maoa-p-arg454 (accessed [today's date]).

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