Is MBL2 p.Pro101= (c.303G>A) pathogenic?

MBL2 p.Pro101= (c.303G>A) is classified Conflicting classifications of pathogenicity in MBL2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-10). Ultra-rare (popmax 0.0184%, mid); Associated with mannose-binding lectin deficiency.

What condition is associated with MBL2 p.Pro101= (c.303G>A)?

MBL2 p.Pro101= (c.303G>A) is associated with mannose-binding lectin deficiency (ClinVar).

How common is MBL2 p.Pro101= (c.303G>A) in the general population?

MBL2 p.Pro101= (c.303G>A) is ultra-rare (popmax 0.0184%, mid) (gnomAD).

MBL2 p.Pro101=

c.303G>A · rs55902142 · VCV878253

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, mid)

Conditions

mannose-binding lectin deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.054	GERP -3.5, phastCons 0.002
Overall
CADD	4.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Middle Eastern · 1/5,434 alleles

Filtering AF 0.00794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00601%

Overall 0.00695% 102/1,467,400 alleles · ultra-rare exomes 88/1,315,206 · genomes 14/152,194 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0184%	5,434
South Asian	0.0148%	6,776
East Asian	0.0128%	7,804
Remaining individualsnot grpmax-eligible	0.0128%	7,839
European (non-Finnish)	0.00708%	14,122
Admixed American	0.00222%	45,022

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: MBL2
Protein: p.Pro101=
Coding: c.303G>A
MANE Select: NM_001378373
dbSNP: rs55902142
Type: single nucleotide variant
Location: chr10:52770671 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 82.59 · 1 PDB
Residue 101: the 'disordered' region

Full MBL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mannose-binding lectin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MBL2 p.Pro101Leu Uncertain significance ★★ ⚠ same residue
MBL2 c.*1135A>G Uncertain significance ★★ same condition
MBL2 c.*1711T>G Uncertain significance ★★ same condition
MBL2 c.*865A>C Uncertain significance ★★ same condition
MBL2 p.Asn136= Uncertain significance ★★ same condition
MBL2 p.Asp219Val Uncertain significance ★★ ⚠ same condition
MBL2 p.Glu245Lys Uncertain significance ★★ ⚠ same condition
MBL2 p.Gly45Ser Uncertain significance ★★ ⚠ 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/mbl2-p-pro101 (accessed [today's date]).

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