MSRB3 p.Pro177=
c.531G>A · rs148675122 · VCV504615
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.499%, eas)
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 -2.3 | GERP -3.7 |
| Overall | ||
| CADD | 3.582 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.499%
East Asian · 224/44,874 alleles
Filtering AF
0.446%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.425%
Overall
0.0214%
346/1,614,138 alleles · rare
exomes 309/1,461,860 · genomes 37/152,278 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.499% | 200 |
| Remaining individualsnot grpmax-eligible | 0.0352% | 2,841 |
| South Asian | 0.0318% | 3,140 |
| European (non-Finnish) | 0.00576% | 17,353 |
| African / African-American | 0.00267% | 37,518 |
| Admixed American | 0.00167% | 60,022 |
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
- MSRB3
- Protein
- p.Pro177=
- Coding
- c.531G>A
- MANE Select
- NM_001031679
- dbSNP
- rs148675122
- Type
- single nucleotide variant
- Location
- chr12:65463295 (GRCh38)
- Gene constraint
- LOEUF 0.961 · pLI 0.08 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.73 · 2 PDB
- Residue 177
- the 'disordered' region
Similar variants
- MSRB3 p.Pro177Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MSRB3 c.-147T>G Likely pathogenic ★★ same type
- MSRB3 p.Cys82Gly Pathogenic/Likely pathogenic ★★ same type
- MSRB3 c.-118C>A Uncertain significance ★★ ⚠ same type
- MSRB3 c.-118C>G Uncertain significance ★★ ⚠ same type
- MSRB3 c.-130C>T Uncertain significance ★★ ⚠ same type
- MSRB3 p.Ala162Val Uncertain significance ★★ ⚠ same type
- MSRB3 p.Ala168Thr 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/msrb3-p-pro177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown