Is MANBA p.Pro730Arg (c.2189C>G) pathogenic?

MANBA p.Pro730Arg (c.2189C>G) is classified Likely benign in MANBA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-01-01). AlphaMissense: likely benign (0.2821); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with MANBA p.Pro730Arg (c.2189C>G)?

MANBA p.Pro730Arg (c.2189C>G) is associated with intellectual disability (ClinVar).

How common is MANBA p.Pro730Arg (c.2189C>G) in the general population?

MANBA p.Pro730Arg (c.2189C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MANBA p.Pro730Arg (c.2189C>G)?

AlphaMissense predicts likely benign (score 0.2821) — an in-silico prediction, not a clinical call.

MANBA p.Pro730Arg

c.2189C>G · rs1729558557 · VCV975743

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2821 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.2821	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -11.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 129 kb · p 0.31 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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: MANBA
Protein: p.Pro730Arg
Coding: c.2189C>G
MANE Select: NM_005908
dbSNP: rs1729558557
Type: single nucleotide variant
Location: chr4:102635014 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 730: a UniProt-annotated variant site (in mansb; complete loss of enzyme activity)

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MANBA p.Pro730Ala Uncertain significance ★ ⚠ same residue
MANBA p.Pro730= Likely benign ★ same residue
MANBA c.2416-3C>T Uncertain significance ★★ same condition
MANBA p.Arg638Cys Uncertain significance ★ ⚠ same condition
MANBA p.Arg641His Conflicting classifications of pathogenicity ★ ⚠ same condition
MANBA p.Ile266Val Likely benign ★ same condition
MANBA p.Leu749Ile Likely benign same condition
MANBA c.1112+1G>T Likely pathogenic ★★ 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/manba-p-pro730arg (accessed [today's date]).

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