Is MASP2 p.Pro52Ser (c.154C>T) pathogenic?

MASP2 p.Pro52Ser (c.154C>T) is classified Uncertain significance in MASP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.1824); Very rare (popmax 0.00354%, sas); Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Pro52Ser (c.154C>T)?

MASP2 p.Pro52Ser (c.154C>T) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

How common is MASP2 p.Pro52Ser (c.154C>T) in the general population?

MASP2 p.Pro52Ser (c.154C>T) is very rare (popmax 0.00354%, sas) (gnomAD).

How is Immunodeficiency due to MASP-2 deficiency inherited?

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

What do computational predictors say about MASP2 p.Pro52Ser (c.154C>T)?

AlphaMissense predicts likely benign (score 0.1824) — an in-silico prediction, not a clinical call.

MASP2 p.Pro52Ser

c.154C>T · rs570974459 · VCV875840

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00354%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

immunodeficiency due to MASP-2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1824	likely benign
REVEL	0.454	indeterminate
SaProt	LLR -10.21	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.39 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00354% South Asian · 3/84,864 alleles

Filtering AF 0.000939% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00046%

Overall 0.00096% 15/1,561,782 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00354%	28,288
East Asian	0.00238%	41,940
Remaining individualsnot grpmax-eligible	0.00165%	60,520
European (non-Finnish)	0.000868%	115,267

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.Pro52Ser
Coding: c.154C>T
MANE Select: NM_006610
dbSNP: rs570974459
Type: single nucleotide variant
Location: chr1:11046971 (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 52: 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-pro52ser (accessed [today's date]).

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