Is MASP2 p.Ala438= (c.1314C>T) pathogenic?

MASP2 p.Ala438= (c.1314C>T) is classified Uncertain significance in MASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00272%, nfe); Associated with immunodeficiency due to MASP-2 deficiency.

What condition is associated with MASP2 p.Ala438= (c.1314C>T)?

MASP2 p.Ala438= (c.1314C>T) is associated with immunodeficiency due to MASP-2 deficiency (ClinVar).

How common is MASP2 p.Ala438= (c.1314C>T) in the general population?

MASP2 p.Ala438= (c.1314C>T) is very rare (popmax 0.00272%, nfe) (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.Ala438=

c.1314C>T · rs199953319 · VCV874848

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00272%, nfe)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -1.6	GERP -3.3
Overall
CADD	0.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00272% European (non-Finnish) · 32/1,175,822 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.0175% 281/1,605,742 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.385%	260
European (non-Finnish)grpmax	0.00272%	36,744
African / African-American	0.00268%	37,287
Remaining individualsnot grpmax-eligible	0.00161%	62,080

Finnish 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.Ala438=
Coding: c.1314C>T
MANE Select: NM_007375 · reported on NM_006610
dbSNP: rs199953319
Type: single nucleotide variant
Location: chr1:11027632 (GRCh38)

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

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-ala438 (accessed [today's date]).

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