Is MANBA p.Arg373= (c.1119G>T) pathogenic?

MANBA p.Arg373= (c.1119G>T) is classified Likely benign in MANBA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). Very rare (popmax 0.000522%, nfe); Associated with beta-mannosidosis.

What condition is associated with MANBA p.Arg373= (c.1119G>T)?

MANBA p.Arg373= (c.1119G>T) is associated with beta-mannosidosis (ClinVar).

How common is MANBA p.Arg373= (c.1119G>T) in the general population?

MANBA p.Arg373= (c.1119G>T) is very rare (popmax 0.000522%, nfe) (gnomAD).

How is Beta-mannosidosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MANBA p.Arg373=

c.1119G>T · rs1288397411 · VCV2742709

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000522%, nfe)

Conditions

beta-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -3.3
Overall
CADD	5.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000522% European (non-Finnish) · 6/1,149,346 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000123%

Overall 0.00038% 6/1,579,952 alleles · very rare exomes 5/1,428,086 · genomes 1/151,866 · joint denominator

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: MANBA
Protein: p.Arg373=
Coding: c.1119G>T
MANE Select: NM_005908
dbSNP: rs1288397411
Type: single nucleotide variant
Location: chr4:102671392 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05

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

Disease context

beta-mannosidosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Beta-mannosidosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

MANBA p.Arg373Gln Uncertain significance ★★ ⚠ same residue
MANBA p.Arg373Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
MANBA c.1112+1G>T Likely pathogenic ★★ same condition
MANBA c.1231-1G>A Likely pathogenic ★★ same condition
MANBA c.1704+1G>T Likely pathogenic ★★ same condition
MANBA c.2158-2A>G Pathogenic ★★ same condition
MANBA c.273-1G>A Likely pathogenic ★★ same condition
MANBA c.378+1G>A Likely pathogenic ★★ 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/manba-p-arg373 (accessed [today's date]).

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