MSRB3 p.Val174=
c.522C>T · rs370488628 · VCV504948
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 | GERP -3.1 |
| Overall | ||
| CADD | 6.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,068 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00161%
26/1,613,984 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,178 |
| Admixed American | 0.005% | 19,997 |
| African / African-American | 0.00401% | 24,963 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish) | 0.0011% | 90,773 |
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.Val174=
- Coding
- c.522C>T
- MANE Select
- NM_001031679
- dbSNP
- rs370488628
- Type
- single nucleotide variant
- Location
- chr12:65463286 (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 174
- the 'disordered' region
Similar variants
- 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
- 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-val174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown