Is MAOA p.Arg129= (c.385A>C) pathogenic?

MAOA p.Arg129= (c.385A>C) is classified Benign in MAOA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Common (popmax 49.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with MAOA p.Arg129= (c.385A>C)?

MAOA p.Arg129= (c.385A>C) is associated with Inborn genetic diseases, Brunner syndrome (ClinVar).

MAOA p.Arg129=

Q: How common is MAOA p.Arg129= (c.385A>C) in the general population?

MAOA p.Arg129= (c.385A>C) is common (popmax 49.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.385A>C · rs1800464 · VCV129585

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 49.6%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -0.37	GERP -5.5, phastCons 0.032
Overall
CADD	4.714	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 49.6% African / African-American · 28,042/56,506 alleles

Filtering AF 49.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.9%

Overall 6.4% 76,739/1,199,692 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	49.6%	2
Middle Eastern	8.81%	11
Ashkenazi Jewishnot grpmax-eligible	8.27%	12
Remaining individualsnot grpmax-eligible	7.48%	13
Admixed American	5.35%	19
European (non-Finnish)	4.33%	23
South Asian	2.54%	39
Finnishnot grpmax-eligible	1.56%	64
Amishnot grpmax-eligible	1.32%	76
East Asian	0.00593%	16,864

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: MAOA
Protein: p.Arg129=
Coding: c.385A>C
MANE Select: NM_000240
dbSNP: rs1800464
Type: single nucleotide variant
Location: chrX:43711950 (GRCh38)
Structure: AlphaFold pLDDT 97.09 · 4 PDB
Residue 129: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Brunner syndrome

Similar variants

MAOA p.Arg129Trp 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-arg129 (accessed [today's date]).

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