Is MASP1 p.Pro623= (c.1869C>T) pathogenic?

MASP1 p.Pro623= (c.1869C>T) is classified Likely benign in MASP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-22). Ultra-rare (popmax 0.0157%, nfe); Associated with 3MC syndrome 1.

What condition is associated with MASP1 p.Pro623= (c.1869C>T)?

MASP1 p.Pro623= (c.1869C>T) is associated with 3MC syndrome 1 (ClinVar).

How common is MASP1 p.Pro623= (c.1869C>T) in the general population?

MASP1 p.Pro623= (c.1869C>T) is ultra-rare (popmax 0.0157%, nfe) (gnomAD).

MASP1 p.Pro623=

c.1869C>T · rs775726494 · VCV707615

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, nfe)

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 -11	GERP -5.8
Overall
CADD	0.201	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0157% European (non-Finnish) · 185/1,180,054 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0122% 197/1,614,092 alleles · ultra-rare exomes 179/1,461,868 · genomes 18/152,224 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0157%	6,379
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,464

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.Pro623=
Coding: c.1869C>T
MANE Select: NM_139125
dbSNP: rs775726494
Type: single nucleotide variant
Location: chr3:187236002 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 9 PDB
Residue 623: 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

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-pro623 (accessed [today's date]).

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