Is MANBA p.Phe702fs (c.2102_2103insAT) pathogenic?

MANBA p.Phe702fs (c.21022103insAT) is classified Pathogenic in MANBA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). Absent from gnomAD; Associated with beta-mannosidosis.

What condition is associated with MANBA p.Phe702fs (c.2102_2103insAT)?

MANBA p.Phe702fs (c.2102_2103insAT) is associated with beta-mannosidosis (ClinVar).

How common is MANBA p.Phe702fs (c.2102_2103insAT) in the general population?

MANBA p.Phe702fs (c.2102_2103insAT) is absent from gnomAD (gnomAD).

How is Beta-mannosidosis inherited?

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

MANBA p.Phe702fs

c.2102_2103insAT · rs2476721403 · VCV2709615

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

beta-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 15 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.55	GERP -4.9

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MANBA
Protein: p.Phe702fs
Coding: c.2102_2103insAT
MANE Select: NM_005908
dbSNP: rs2476721403
Type: Insertion
Location: chr4:102635919 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.05
Residue 702: 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.Ser505fs Pathogenic/Likely pathogenic ★★ same condition
MANBA p.Asn216delinsArgGluGluProArgTrpProAsnArgAsnSerSerGlyLeuGlnLeuProAlaTer Pathogenic ★ same condition
MANBA p.Thr701delinsMetTer Pathogenic ★ same condition
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

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-phe702fs (accessed [today's date]).

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