Is MASP2 p.Ser185= (c.555C>T) pathogenic?

MASP2 p.Ser185= (c.555C>T) is classified Benign in MASP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). Common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Ser185= (c.555C>T)?

MASP2 p.Ser185= (c.555C>T) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

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.Ser185=

Q: How common is MASP2 p.Ser185= (c.555C>T) in the general population?

MASP2 p.Ser185= (c.555C>T) is common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.555C>T · rs78775425 · VCV291799

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 8.07%, afr) — too common for a highly-penetrant pathogenic allele

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 -12	GERP -3.5
Overall
CADD	0.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.07% African / African-American · 6,038/74,778 alleles

Filtering AF 7.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.83%

Overall 0.437% 6,983/1,598,482 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.07%	12
Remaining individualsnot grpmax-eligible	0.559%	179
Middle Eastern	0.523%	191
Admixed American	0.449%	223
Ashkenazi Jewishnot grpmax-eligible	0.175%	573
South Asian	0.0271%	3,687
European (non-Finnish)	0.0199%	5,015
East Asian	0.00449%	22,257
Finnishnot grpmax-eligible	0.00321%	31,120

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.Ser185=
Coding: c.555C>T
MANE Select: NM_006610
dbSNP: rs78775425
Type: single nucleotide variant
Location: chr1:11043525 (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 185: the cub 2 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-ser185 (accessed [today's date]).

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