Is MANBA p.Ser712= (c.2136G>A) pathogenic?

MANBA p.Ser712= (c.2136G>A) is classified Benign/Likely benign in MANBA (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.674%, afr); Associated with beta-mannosidosis.

What condition is associated with MANBA p.Ser712= (c.2136G>A)?

MANBA p.Ser712= (c.2136G>A) is associated with beta-mannosidosis (ClinVar).

How common is MANBA p.Ser712= (c.2136G>A) in the general population?

MANBA p.Ser712= (c.2136G>A) is rare (popmax 0.674%, afr) (gnomAD).

How is Beta-mannosidosis inherited?

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

MANBA p.Ser712=

c.2136G>A · rs149687835 · VCV786074

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.674%, afr)

Conditions

beta-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.46	donor loss, 21 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -5.6	GERP -4.9
Overall
CADD	0.191	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.674% African / African-American · 505/74,968 alleles

Filtering AF 0.625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.606%

Overall 0.0543% 875/1,612,480 alleles · rare exomes 527/1,460,230 · genomes 348/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.674%	148
Admixed American	0.157%	638
Remaining individualsnot grpmax-eligible	0.0993%	1,008
Middle Eastern	0.099%	1,010
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,345
European (non-Finnish)	0.0154%	6,476
East Asian	0.00446%	22,444
South Asian	0.0022%	45,519

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.Ser712=
Coding: c.2136G>A
MANE Select: NM_005908
dbSNP: rs149687835
Type: single nucleotide variant
Location: chr4:102635886 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 712: 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 p.Ser712Leu Uncertain significance ★ ⚠ 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
MANBA c.549+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-ser712 (accessed [today's date]).

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