Is MASP2 p.Ser493= (c.1479C>T) pathogenic?

MASP2 p.Ser493= (c.1479C>T) is classified Benign/Likely benign in MASP2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Common (popmax 86.9%, eas) — too common for a highly-penetrant pathogenic allele.

MASP2 p.Ser493=

Q: How common is MASP2 p.Ser493= (c.1479C>T) in the general population?

MASP2 p.Ser493= (c.1479C>T) is common (popmax 86.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1479C>T · rs1782455 · VCV291781

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 86.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.68	GERP -3
Overall
CADD	1.746	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 86.9% East Asian · 39,003/44,866 alleles

Filtering AF 86.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.9%

Overall 80.6% 1,301,047/1,613,586 alleles · common exomes 1,196,308/1,461,602 · genomes 104,739/151,984 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	89%	1
East Asiangrpmax	86.9%	1
European (non-Finnish)	83.6%	1
Finnishnot grpmax-eligible	83.1%	1
Admixed American	80.3%	1
Remaining individualsnot grpmax-eligible	79.3%	1
South Asian	79.1%	1
Middle Eastern	75.6%	1
Ashkenazi Jewishnot grpmax-eligible	73.2%	1
African / African-American	33.8%	3

Amish 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.Ser493=
Coding: c.1479C>T
MANE Select: NM_006610
dbSNP: rs1782455
Type: single nucleotide variant
Location: chr1:11027467 (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 493: an α-helix; the peptidase s1 domain

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

Similar variants

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
MASP2 p.Asp75Asn Uncertain significance ★★ ⚠ same type
MASP2 p.Cys396Tyr 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-ser493 (accessed [today's date]).

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