Is MAOB p.Glu366Asp (c.1098A>C) pathogenic?

MAOB p.Glu366Asp (c.1098A>C) is classified Uncertain significance in MAOB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1418); Very rare (popmax 0.00304%, nfe).

How common is MAOB p.Glu366Asp (c.1098A>C) in the general population?

MAOB p.Glu366Asp (c.1098A>C) is very rare (popmax 0.00304%, nfe) (gnomAD).

What do computational predictors say about MAOB p.Glu366Asp (c.1098A>C)?

AlphaMissense predicts likely benign (score 0.1418) — an in-silico prediction, not a clinical call.

MAOB p.Glu366Asp

c.1098A>C · VCV3542530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00304%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1418	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -8.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.92	GERP -3.6, phastCons 0.002
Regional constraint	o/e 0.87	unconstrained · MANE · 115 kb · p 0.0071 · regional, not allelic
Overall
CADD	12.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00304% European (non-Finnish) · 27/889,203 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00257% 28/1,089,978 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00304%	32,933
Remaining individualsnot grpmax-eligible	0.00211%	47,323

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: MAOB
Protein: p.Glu366Asp
Coding: c.1098A>C
MANE Select: NM_000898
Type: single nucleotide variant
Location: chrX:43778721 (GRCh38)
Structure: AlphaFold pLDDT 95.68 · 57 PDB
Residue 366: an α-helix

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

Similar variants

MAOB p.Ala161Ser Uncertain significance ★★ ⚠ same type
MAOB p.Ala322Thr Uncertain significance ★ ⚠ same type
MAOB p.Arg100Ser Uncertain significance ★ ⚠ same type
MAOB p.Arg220Gln Uncertain significance ★ ⚠ same type
MAOB p.Arg242Lys Uncertain significance ★ ⚠ same type
MAOB p.Arg282Lys Uncertain significance ★ ⚠ same type
MAOB p.Arg288His Uncertain significance ★ ⚠ same type
MAOB p.Arg36Trp Uncertain significance ★ ⚠ same type

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/maob-p-glu366asp (accessed [today's date]).

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