Is MANBA p.Val770= (c.2310G>A) pathogenic?

MANBA p.Val770= (c.2310G>A) is classified Likely benign in MANBA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-10). Ultra-rare (popmax 0.0703%, sas); Associated with beta-mannosidosis.

What condition is associated with MANBA p.Val770= (c.2310G>A)?

MANBA p.Val770= (c.2310G>A) is associated with beta-mannosidosis (ClinVar).

How common is MANBA p.Val770= (c.2310G>A) in the general population?

MANBA p.Val770= (c.2310G>A) is ultra-rare (popmax 0.0703%, sas) (gnomAD).

How is Beta-mannosidosis inherited?

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

MANBA p.Val770=

c.2310G>A · rs552616448 · VCV2971677

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, sas)

Conditions

beta-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss, 20 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.37	GERP -1.6, phastCons 0.024
Overall
CADD	5.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% South Asian · 64/91,088 alleles

Filtering AF 0.0564% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00396% 64/1,614,222 alleles · ultra-rare

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.Val770=
Coding: c.2310G>A
MANE Select: NM_005908
dbSNP: rs552616448
Type: single nucleotide variant
Location: chr4:102634893 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 770: 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

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 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
MANBA c.549+1G>A Likely pathogenic ★★ same condition
MANBA c.550-1G>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-val770 (accessed [today's date]).

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