Is MASP2 p.Pro20= (c.60G>A) pathogenic?

MASP2 p.Pro20= (c.60G>A) is classified Benign/Likely benign in MASP2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-04-06). Low-frequency (popmax 1.91%, afr); Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Pro20= (c.60G>A)?

MASP2 p.Pro20= (c.60G>A) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

How common is MASP2 p.Pro20= (c.60G>A) in the general population?

MASP2 p.Pro20= (c.60G>A) is low-frequency (popmax 1.91%, afr) (gnomAD).

How is Immunodeficiency due to MASP-2 deficiency inherited?

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

MASP2 p.Pro20=

c.60G>A · rs61432273 · VCV876831

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, afr)

Conditions

immunodeficiency due to MASP-2 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 -14	GERP -2.7
Overall
CADD	0.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.91% African / African-American · 1,393/72,844 alleles

Filtering AF 1.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.8%

Overall 0.115% 1,778/1,549,624 alleles · low-frequency exomes 917/1,398,374 · genomes 861/151,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.91%	52
Admixed American	0.216%	463
Remaining individualsnot grpmax-eligible	0.19%	527
Middle Eastern	0.152%	656
European (non-Finnish)	0.0129%	7,748
East Asian	0.0049%	20,415
South Asian	0.00238%	42,015

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: MASP2
Protein: p.Pro20=
Coding: c.60G>A
MANE Select: NM_006610
dbSNP: rs61432273
Type: single nucleotide variant
Location: chr1:11047065 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.73 · 10 PDB
Residue 20: the cub 1 domain

Full MASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency due to MASP-2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to MASP-2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent

Similar variants

MASP2 p.Pro20Leu Uncertain significance ★ ⚠ same residue
MASP2 p.Arg376Ter Likely pathogenic ★★ same condition
MASP2 p.Ala149Val Uncertain significance ★★ ⚠ same condition
MASP2 p.Arg29His Uncertain significance ★★ ⚠ same condition
MASP2 p.Arg58Cys Uncertain significance ★★ ⚠ same condition
MASP2 p.Asp75Asn Uncertain significance ★★ ⚠ same condition
MASP2 p.Cys396Tyr Uncertain significance ★★ ⚠ same condition
MASP2 p.Gly34Ser 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/masp2-p-pro20 (accessed [today's date]).

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