Is MASP2 p.Arg563= (c.1689G>A) pathogenic?

MASP2 p.Arg563= (c.1689G>A) is classified Likely benign in MASP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-06-11). Very rare (popmax 0.00169%, nfe); Associated with MASP2-related disorder.

What condition is associated with MASP2 p.Arg563= (c.1689G>A)?

MASP2 p.Arg563= (c.1689G>A) is associated with MASP2-related disorder (ClinVar).

How common is MASP2 p.Arg563= (c.1689G>A) in the general population?

MASP2 p.Arg563= (c.1689G>A) is very rare (popmax 0.00169%, nfe) (gnomAD).

MASP2 p.Arg563=

c.1689G>A · rs766503914 · VCV3033229

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

MASP2-related disorder

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 -0.69	GERP -0.67
Overall
CADD	6.601	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,038 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00142% 23/1,614,038 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)grpmax	0.00169%	59,002

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.Arg563=
Coding: c.1689G>A
MANE Select: NM_006610
dbSNP: rs766503914
Type: single nucleotide variant
Location: chr1:11027257 (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 563: the peptidase s1 domain

Full MASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MASP2-related disorder

Similar variants

MASP2 p.Val311Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
MASP2 p.Ala619= Likely benign same condition
MASP2 p.Arg609= Likely benign same condition
MASP2 p.Gly464Ala Benign same condition
MASP2 p.Ser119= Likely benign same condition
MASP2 p.Thr549= Likely benign same condition
MASP2 c.1087+8_1087+10del Uncertain significance ★ same condition
MASP2 p.Arg376Ter Likely pathogenic ★★ same type

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-arg563 (accessed [today's date]).

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