MASP2 p.Val649=
c.1947G>T · rs148865407 · VCV2638215
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00563%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.018 | GERP -3.3, phastCons 0.75 |
| Overall | ||
| CADD | 5.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00563%
European (non-Finnish) · 66/1,172,388 alleles
Filtering AF
0.00454%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00414%
Overall
0.00438%
70/1,597,878 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00563% | 17,763 |
| Finnishnot grpmax-eligible | 0.00315% | 31,756 |
| Admixed American | 0.00175% | 57,270 |
| African / African-American | 0.00134% | 74,476 |
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.Val649=
- Coding
- c.1947G>T
- MANE Select
- NM_006610
- dbSNP
- rs148865407
- Type
- single nucleotide variant
- Location
- chr1:11026999 (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 649
- a β-strand; a disulfide bond; the peptidase s1 domain
Similar variants
- MASP2 p.Val649Ala Uncertain significance ★ ⚠ same residue
- 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
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-val649 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown