Is MAN2B1 p.Pro571= (c.1713C>T) pathogenic?

MAN2B1 p.Pro571= (c.1713C>T) is classified Conflicting classifications of pathogenicity in MAN2B1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-09). Ultra-rare (popmax 0.0165%, mid); Associated with alpha-mannosidosis.

What condition is associated with MAN2B1 p.Pro571= (c.1713C>T)?

MAN2B1 p.Pro571= (c.1713C>T) is associated with alpha-mannosidosis (ClinVar).

How common is MAN2B1 p.Pro571= (c.1713C>T) in the general population?

MAN2B1 p.Pro571= (c.1713C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Alpha-mannosidosis inherited?

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

MAN2B1 p.Pro571=

c.1713C>T · rs747081586 · VCV716707

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

alpha-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.054	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.13	GERP -2.8, phastCons 0.13
Overall
CADD	8.445	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,072 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000558% 9/1,613,208 alleles · ultra-rare exomes 7/1,461,044 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,072
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
Admixed American	0.00167%	59,950
South Asian	0.0011%	91,068
European (non-Finnish)	0.000424%	235,896

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: MAN2B1
Protein: p.Pro571=
Coding: c.1713C>T
MANE Select: NM_000528
dbSNP: rs747081586
Type: single nucleotide variant
Location: chr19:12655811 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78
Residue 571: 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.Pro571His Uncertain significance ★ ⚠ 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
MAN2B1 c.1528-1G>A Pathogenic/Likely pathogenic ★★ same condition
MAN2B1 c.1528-1G>T 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-pro571 (accessed [today's date]).

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