MSRB3 p.Ala162=
c.486G>A · rs35393316 · VCV178616
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.813%, afr)
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 -3.7 |
| Overall | ||
| CADD | 5.422 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.813%
African / African-American · 610/75,022 alleles
Filtering AF
0.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.738%
Overall
0.0439%
708/1,614,162 alleles · rare
exomes 359/1,461,888 · genomes 349/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.813% | 123 |
| Admixed American | 0.0466% | 2,144 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| East Asian | 0.00446% | 22,442 |
| European (non-Finnish) | 0.00356% | 28,096 |
| South Asian | 0.0022% | 45,536 |
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.Ala162=
- Coding
- c.486G>A
- MANE Select
- NM_001031679
- dbSNP
- rs35393316
- Type
- single nucleotide variant
- Location
- chr12:65463250 (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 162
- the msrb domain; an α-helix
Similar variants
- MSRB3 p.Ala162Val Uncertain significance ★★ ⚠ 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.Ala168Thr Uncertain significance ★★ ⚠ same type
- MSRB3 p.Arg144His 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-ala162 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown