Is MASP2 p.Pro53= (c.159C>T) pathogenic?

MASP2 p.Pro53= (c.159C>T) is classified Uncertain significance in MASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00571%, amr); Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Pro53= (c.159C>T)?

MASP2 p.Pro53= (c.159C>T) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

How common is MASP2 p.Pro53= (c.159C>T) in the general population?

MASP2 p.Pro53= (c.159C>T) is very rare (popmax 0.00571%, amr) (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.Pro53=

c.159C>T · rs376802078 · VCV291812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00571%, amr)

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 -9.2	GERP -3.8
Overall
CADD	3.252	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00571% Admixed American · 3/52,520 alleles

Filtering AF 0.00152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000921%

Overall 0.00474% 74/1,562,750 alleles · very rare exomes 63/1,410,550 · genomes 11/152,200 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.139%	719
Remaining individualsnot grpmax-eligible	0.00991%	10,089
Admixed Americangrpmax	0.00571%	17,507
African / African-American	0.00272%	36,821
South Asian	0.00235%	42,485
European (non-Finnish)	0.00173%	57,664
Finnishnot grpmax-eligible	0.00166%	60,072

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: MASP2
Protein: p.Pro53=
Coding: c.159C>T
MANE Select: NM_006610
dbSNP: rs376802078
Type: single nucleotide variant
Location: chr1:11046966 (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 53: 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.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
MASP2 p.Gly635Arg 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-pro53 (accessed [today's date]).

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