Is MAOA p.Pro275= (c.825G>A) pathogenic?

MAOA p.Pro275= (c.825G>A) is classified Conflicting classifications of pathogenicity in MAOA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-16). Rare (popmax 0.432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MAOA p.Pro275= (c.825G>A)?

MAOA p.Pro275= (c.825G>A) is associated with Inborn genetic diseases, Brunner syndrome (ClinVar).

How common is MAOA p.Pro275= (c.825G>A) in the general population?

MAOA p.Pro275= (c.825G>A) is rare (popmax 0.432%, nfe) (gnomAD).

MAOA p.Pro275=

c.825G>A · rs138703731 · VCV198701

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.432%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.3	GERP -5.5
Overall
CADD	0.727	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.432% European (non-Finnish) · 3,865/894,832 alleles

Filtering AF 0.421% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.416%

Overall 0.366% 4,430/1,209,353 alleles · rare exomes 4,165/1,097,719 · genomes 265/111,634 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.49%	204
European (non-Finnish)grpmax	0.432%	232
Middle Eastern	0.345%	290
Remaining individualsnot grpmax-eligible	0.338%	296
South Asian	0.296%	338
Admixed American	0.158%	635
African / African-American	0.0561%	1,784
Finnishnot grpmax-eligible	0.015%	6,649
East Asian	0.00593%	16,862

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro275=
Coding: c.825G>A
MANE Select: NM_000240
dbSNP: rs138703731
Type: single nucleotide variant
Location: chrX:43731723 (GRCh38)
Structure: AlphaFold pLDDT 97.09 · 4 PDB
Residue 275: 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.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
MAOA p.Glu58Lys 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-pro275 (accessed [today's date]).

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