Is MASP1 p.Ser445= (c.1335C>T) pathogenic?

MASP1 p.Ser445= (c.1335C>T) is classified Benign/Likely benign in MASP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Common (popmax 19.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with 3MC syndrome 1.

What condition is associated with MASP1 p.Ser445= (c.1335C>T)?

MASP1 p.Ser445= (c.1335C>T) is associated with 3MC syndrome 1 (ClinVar).

MASP1 p.Ser445=

Q: How common is MASP1 p.Ser445= (c.1335C>T) in the general population?

MASP1 p.Ser445= (c.1335C>T) is common (popmax 19.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1335C>T · rs3774268 · VCV1164249

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 19.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

3MC syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.1	GERP 0.78, phastCons 1
Overall
CADD	7.058	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.4% African / African-American · 14,537/74,958 alleles

Filtering AF 19.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 19%

Overall 14% 226,087/1,613,894 alleles · common exomes 203,070/1,461,758 · genomes 23,017/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	19.4%	5
Middle Eastern	15.7%	6
Amishnot grpmax-eligible	14.8%	7
Admixed American	14.7%	7
Remaining individualsnot grpmax-eligible	14.6%	7
Ashkenazi Jewishnot grpmax-eligible	14.3%	7
European (non-Finnish)	13.9%	7
South Asian	13%	8
Finnishnot grpmax-eligible	11.7%	9
East Asian	11.5%	9

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.Ser445=
Coding: c.1335C>T
MANE Select: NM_139125
dbSNP: rs3774268
Type: single nucleotide variant
Location: chr3:187236536 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 9 PDB
Residue 445: a UniProt-annotated variant site (in 3mc1)

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

Disease context

3MC syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MASP1 p.Lys337Ter Pathogenic/Likely pathogenic ★★ same condition
MASP1 p.Arg503His Uncertain significance ★★ same condition
MASP1 p.Glu105Asp Uncertain significance ★★ ⚠ same condition
MASP1 p.Gly592Ser Uncertain significance ★★ same condition
MASP1 p.Gly665Ser Uncertain significance ★★ same condition
MASP1 p.Leu304Ile Uncertain significance ★★ ⚠ same condition
MASP1 p.Pro241Leu Uncertain significance ★★ ⚠ same condition
MASP1 p.Pro258Leu 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-ser445 (accessed [today's date]).

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