Is MASP2 p.Arg178Ser (c.532C>A) pathogenic?

MASP2 p.Arg178Ser (c.532C>A) is classified Uncertain significance in MASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-12). AlphaMissense: likely benign (0.2736); Very rare (popmax 0.00136%, nfe).

How common is MASP2 p.Arg178Ser (c.532C>A) in the general population?

MASP2 p.Arg178Ser (c.532C>A) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about MASP2 p.Arg178Ser (c.532C>A)?

AlphaMissense predicts likely benign (score 0.2736) — an in-silico prediction, not a clinical call.

MASP2 p.Arg178Ser

c.532C>A · VCV3293377

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2736	likely benign
REVEL	0.544	indeterminate
SaProt	LLR -11.23	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 6.5	GERP -0.48, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 20 kb · p 0.39 · regional, not allelic
Overall
CADD	24.2	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 0.00136% European (non-Finnish) · 16/1,179,948 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00112% 18/1,613,052 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)grpmax	0.00136%	73,747
South Asian	0.0011%	91,088

Remaining individuals 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.Arg178Ser
Coding: c.532C>A
MANE Select: NM_006610
Type: single nucleotide variant
Location: chr1:11045420 (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 178: a disulfide bond; the egf-like; calcium-binding domain

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

Similar variants

MASP2 p.Arg178Cys Uncertain significance ★ ⚠ same residue
MASP2 p.Arg178His Likely benign ★ same residue
MASP2 p.Arg376Ter Likely pathogenic ★★ same type
TARDBP p.Gly294Val Pathogenic/Likely pathogenic ★★ ⚠ same type
MASP2 p.Ala149Val Uncertain significance ★★ ⚠ same type
MASP2 p.Ala169Gly Uncertain significance ★★ ⚠ same type
MASP2 p.Arg29His Uncertain significance ★★ ⚠ same type
MASP2 p.Arg58Cys Uncertain significance ★★ ⚠ 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-arg178ser (accessed [today's date]).

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