MASP1 p.Pro462=
c.1386G>A · rs35384947 · VCV463035
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.48%, afr)
Conditions
1
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 -20 | GERP -5.6 |
| Overall | ||
| CADD | 0.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.48%
African / African-American · 3,364/75,014 alleles
Filtering AF
4.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.31%
Overall
0.238%
3,843/1,614,034 alleles · low-frequency
exomes 1,955/1,461,764 · genomes 1,888/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.48% | 22 |
| Remaining individualsnot grpmax-eligible | 0.275% | 363 |
| Admixed American | 0.247% | 405 |
| Middle Eastern | 0.198% | 505 |
| Ashkenazi Jewishnot grpmax-eligible | 0.115% | 871 |
| East Asian | 0.111% | 897 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00415% | 24,082 |
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.Pro462=
- Coding
- c.1386G>A
- MANE Select
- NM_139125
- dbSNP
- rs35384947
- Type
- single nucleotide variant
- Location
- chr3:187236485 (GRCh38)
- Gene constraint
- LOEUF 0.874 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.50 · 9 PDB
- Residue 462
- a UniProt-annotated variant site (in 3mc1); the peptidase s1 domain
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-pro462 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown