Is MAOB p.Leu22Pro (c.65T>C) pathogenic?

MAOB p.Leu22Pro (c.65T>C) is classified Uncertain significance in MAOB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9712); Absent from gnomAD v4.1.

How common is MAOB p.Leu22Pro (c.65T>C) in the general population?

MAOB p.Leu22Pro (c.65T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAOB p.Leu22Pro (c.65T>C)?

AlphaMissense predicts likely pathogenic (score 0.9712) — an in-silico prediction, not a clinical call.

MAOB p.Leu22Pro

c.65T>C · VCV4549230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9712	likely pathogenic · top 9% in MAOB
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -12.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 115 kb · p 0.0071 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

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: MAOB
Protein: p.Leu22Pro
Coding: c.65T>C
MANE Select: NM_000898
Type: single nucleotide variant
Location: chrX:43843746 (GRCh38)
Structure: AlphaFold pLDDT 95.68 · 57 PDB
Residue 22: 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-leu22pro (accessed [today's date]).

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