Is MASP1 p.Arg596Ser (c.1788G>T) pathogenic?

MASP1 p.Arg596Ser (c.1788G>T) is classified Uncertain significance in MASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-21). AlphaMissense: ambiguous (0.3957); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with MASP1 p.Arg596Ser (c.1788G>T)?

MASP1 p.Arg596Ser (c.1788G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MASP1 p.Arg596Ser (c.1788G>T) in the general population?

MASP1 p.Arg596Ser (c.1788G>T) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MASP1 p.Arg596Ser (c.1788G>T)?

AlphaMissense predicts ambiguous (score 0.3957) — an in-silico prediction, not a clinical call.

MASP1 p.Arg596Ser

c.1788G>T · rs768987275 · VCV2213758

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3957	ambiguous
REVEL	0.301	indeterminate
SaProt	LLR -5.02	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -2.3
Overall
CADD	9.423	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 0.00534% African / African-American · 4/74,912 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,614,012 alleles · very rare exomes 20/1,461,852 · genomes 3/152,160 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,728
South Asian	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0016%	62,488
Finnishnot grpmax-eligible	0.00156%	64,030
European (non-Finnish)	0.00119%	84,286

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: MASP1
Protein: p.Arg596Ser
Coding: c.1788G>T
MANE Select: NM_139125 · reported on NM_001879
dbSNP: rs768987275
Type: single nucleotide variant
Location: chr3:187223148 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 9 PDB
Residue 596: a β-strand; a UniProt-annotated variant site (in 3mc1); the peptidase s1 domain

Full MASP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MASP1 p.Arg596Met Uncertain significance ★★ ⚠ same residue
MASP1 p.Arg596Lys Uncertain significance ★ ⚠ same residue
MASP1 p.Ala489Thr Uncertain significance ★★ ⚠ same condition
MASP1 p.Arg119Gln Uncertain significance ★★ ⚠ same condition
MASP1 p.Arg503His Uncertain significance ★★ same condition
MASP1 p.Glu105Asp Uncertain significance ★★ ⚠ same condition
MASP1 p.Glu142Lys Uncertain significance ★★ ⚠ same condition
MASP1 p.Gly656Ser 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/masp1-p-arg596ser (accessed [today's date]).

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