Is MAN2B1 p.Pro705fs (c.2114del) pathogenic?

MAN2B1 p.Pro705fs (c.2114del) is classified Likely pathogenic in MAN2B1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-09-18). Absent from gnomAD; Associated with alpha-mannosidosis.

What condition is associated with MAN2B1 p.Pro705fs (c.2114del)?

MAN2B1 p.Pro705fs (c.2114del) is associated with alpha-mannosidosis (ClinVar).

How common is MAN2B1 p.Pro705fs (c.2114del) in the general population?

MAN2B1 p.Pro705fs (c.2114del) is absent from gnomAD (gnomAD).

How is Alpha-mannosidosis inherited?

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

MAN2B1 p.Pro705fs

c.2114del · rs1555706774 · VCV553884

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

alpha-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 17 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.8	GERP -3.3

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: MAN2B1
Protein: p.Pro705fs
Coding: c.2114del
MANE Select: NM_000528
dbSNP: rs1555706774
Type: Deletion
Location: chr19:12650155 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78
Residue 705: a UniProt-annotated variant site (in mansa); a UniProt-annotated variant site (in mansa; uncertain significance)

Full MAN2B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Alpha-mannosidosis (Orphanet):

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

Similar variants

MAN2B1 p.Pro705Ter Pathogenic ★ same residue
MAN2B1 c.1420-27_1420-3del Likely pathogenic ★★ same condition
MAN2B1 c.763+2_763+8del Likely pathogenic ★★ same condition
MAN2B1 p.Ala44fs Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 p.Ala854fs Pathogenic ★★ same condition
MAN2B1 p.Arg188fs Pathogenic ★★ same condition
MAN2B1 p.Arg760fs Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 p.Asn324fs 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/man2b1-p-pro705fs (accessed [today's date]).

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