MASP2 p.Arg646=
c.1938G>A · VCV4955059
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.561%, sas)
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 -0.47 | GERP -3.3 |
| Overall | ||
| CADD | 1.714 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.561%
South Asian · 497/88,578 alleles
Filtering AF
0.52%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.504%
Overall
0.038%
607/1,599,436 alleles · rare
exomes 555/1,447,112 · genomes 52/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.561% | 178 |
| Remaining individualsnot grpmax-eligible | 0.0857% | 1,167 |
| Middle Eastern | 0.0167% | 5,978 |
| East Asian | 0.0134% | 7,475 |
| African / African-American | 0.00671% | 14,912 |
| Finnishnot grpmax-eligible | 0.00472% | 21,188 |
| European (non-Finnish) | 0.00349% | 28,613 |
| Admixed American | 0.00174% | 57,552 |
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.Arg646=
- Coding
- c.1938G>A
- MANE Select
- NM_006610
- Type
- single nucleotide variant
- Location
- chr1:11027008 (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 646
- a β-strand; the peptidase s1 domain
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-arg646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown