Is MAN2B1 p.Arg613= (c.1839G>A) pathogenic?

MAN2B1 p.Arg613= (c.1839G>A) is classified Likely benign in MAN2B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-14). Absent from gnomAD v4.1; Associated with alpha-mannosidosis.

What condition is associated with MAN2B1 p.Arg613= (c.1839G>A)?

MAN2B1 p.Arg613= (c.1839G>A) is associated with alpha-mannosidosis (ClinVar).

How common is MAN2B1 p.Arg613= (c.1839G>A) in the general population?

MAN2B1 p.Arg613= (c.1839G>A) is absent from gnomAD v4.1 (gnomAD).

How is Alpha-mannosidosis inherited?

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

MAN2B1 p.Arg613=

c.1839G>A · rs2512493183 · VCV2828413

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

alpha-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.141	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	gain · loss 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.37	GERP -0.53, phastCons 0.039
Overall
CADD	9.189	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAN2B1
Protein: p.Arg613=
Coding: c.1839G>A
MANE Select: NM_000528
dbSNP: rs2512493183
Type: single nucleotide variant
Location: chr19:12652452 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78
Residue 613: 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.Arg613Trp Uncertain significance ★★ ⚠ same residue
MAN2B1 p.Arg613Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MAN2B1 p.Arg613fs Likely pathogenic ★ same residue
MAN2B1 c.1026+2T>G Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 c.1109+1G>C Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 c.1527+1G>A Likely pathogenic ★★ same condition
MAN2B1 c.1527+1G>T Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 c.1527+2T>G 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-arg613 (accessed [today's date]).

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