Is MASP2 p.Val77= (c.231C>T) pathogenic?

MASP2 p.Val77= (c.231C>T) is classified Conflicting classifications of pathogenicity in MASP2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-23). Low-frequency (popmax 1.92%, mid); Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Val77= (c.231C>T)?

MASP2 p.Val77= (c.231C>T) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

How common is MASP2 p.Val77= (c.231C>T) in the general population?

MASP2 p.Val77= (c.231C>T) is low-frequency (popmax 1.92%, mid) (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.Val77=

c.231C>T · rs140239262 · VCV291811

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.92%, mid)

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 3.4	GERP -2, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.92% Middle Eastern · 115/6,000 alleles

Filtering AF 1.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.53%

Overall 0.0638% 999/1,565,782 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.92%	52
Admixed American	0.172%	583
Remaining individualsnot grpmax-eligible	0.117%	856
Amishnot grpmax-eligible	0.11%	912
South Asian	0.0598%	1,673
European (non-Finnish)	0.0548%	1,824
African / African-American	0.0473%	2,114
Ashkenazi Jewishnot grpmax-eligible	0.0104%	9,583

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.Val77=
Coding: c.231C>T
MANE Select: NM_006610
dbSNP: rs140239262
Type: single nucleotide variant
Location: chr1:11046894 (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 77: the cub 1 domain; a β-strand

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.Val77Ile 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-val77 (accessed [today's date]).

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