Is MAOA p.Ser227= (c.681C>T) pathogenic?

MAOA p.Ser227= (c.681C>T) is classified Likely benign in MAOA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.0175%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAOA p.Ser227= (c.681C>T)?

MAOA p.Ser227= (c.681C>T) is associated with Inborn genetic diseases, Brunner syndrome (ClinVar).

How common is MAOA p.Ser227= (c.681C>T) in the general population?

MAOA p.Ser227= (c.681C>T) is ultra-rare (popmax 0.0175%, amr) (gnomAD).

MAOA p.Ser227=

c.681C>T · rs758225239 · VCV1537792

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, amr)

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 -2.8	GERP -5.5
Overall
CADD	4.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0175% Admixed American · 8/45,775 alleles

Filtering AF 0.00869% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0063%

Overall 0.00306% 37/1,208,223 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0175%	5,722
South Asian	0.00704%	14,195
African / African-American	0.0035%	28,568
European (non-Finnish)	0.00257%	38,853

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.Ser227=
Coding: c.681C>T
MANE Select: NM_000240
dbSNP: rs758225239
Type: single nucleotide variant
Location: chrX:43731276 (GRCh38)
Structure: AlphaFold pLDDT 97.09 · 4 PDB
Residue 227: 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-ser227 (accessed [today's date]).

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