Is MASP1 p.Ala489= (c.1467G>A) pathogenic?

MASP1 p.Ala489= (c.1467G>A) is classified Benign/Likely benign in MASP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-07-14). Rare (popmax 0.167%, eas); Associated with 3MC syndrome 1.

What condition is associated with MASP1 p.Ala489= (c.1467G>A)?

MASP1 p.Ala489= (c.1467G>A) is associated with 3MC syndrome 1 (ClinVar).

How common is MASP1 p.Ala489= (c.1467G>A) in the general population?

MASP1 p.Ala489= (c.1467G>A) is rare (popmax 0.167%, eas) (gnomAD).

MASP1 p.Ala489=

c.1467G>A · rs149695036 · VCV702778

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, eas)

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 1.1	GERP 0.81, phastCons 1
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% East Asian · 75/44,878 alleles

Filtering AF 0.137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.0123% 198/1,614,196 alleles · rare exomes 167/1,461,890 · genomes 31/152,306 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.167%	598
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0208%	4,809
South Asian	0.0132%	7,590
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
Admixed American	0.00833%	12,006
European (non-Finnish)	0.00729%	13,721
African / African-American	0.00266%	37,524

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.Ala489=
Coding: c.1467G>A
MANE Select: NM_139125
dbSNP: rs149695036
Type: single nucleotide variant
Location: chr3:187236404 (GRCh38)
Gene constraint: LOEUF 0.874 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 9 PDB
Residue 489: an α-helix; 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.Ala489Thr Uncertain significance ★★ ⚠ same residue
MASP1 p.Ala489Val Uncertain significance ★ same residue
MASP1 p.Ala489Glu Likely benign ★ same residue
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

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-ala489 (accessed [today's date]).

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