Is MAN2B1 p.Ser103= (c.309G>A) pathogenic?

MAN2B1 p.Ser103= (c.309G>A) is classified Likely benign in MAN2B1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-14). Very rare (popmax 0.00333%, amr); Associated with alpha-mannosidosis.

What condition is associated with MAN2B1 p.Ser103= (c.309G>A)?

MAN2B1 p.Ser103= (c.309G>A) is associated with alpha-mannosidosis (ClinVar).

How common is MAN2B1 p.Ser103= (c.309G>A) in the general population?

MAN2B1 p.Ser103= (c.309G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Alpha-mannosidosis inherited?

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

MAN2B1 p.Ser103=

c.309G>A · rs1175779934 · VCV1024843

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

alpha-mannosidosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -15	GERP -3.7
Overall
CADD	7.362	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00124% 20/1,614,000 alleles · very rare exomes 19/1,461,854 · genomes 1/152,146 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed Americangrpmax	0.00333%	29,996
African / African-American	0.00267%	37,453
European (non-Finnish)	0.00127%	78,670

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser103=
Coding: c.309G>A
MANE Select: NM_000528
dbSNP: rs1175779934
Type: single nucleotide variant
Location: chr19:12665479 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.78
Residue 103: a UniProt-annotated variant site (in mansa)

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.Ser103Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
MAN2B1 p.Ser103fs 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
MAN2B1 c.1528-1G>A Pathogenic/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-ser103 (accessed [today's date]).

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