MSRB3 p.Lys78=
c.234A>G · rs143333399 · VCV504613
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.099%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.035 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.05 | GERP -3.5, phastCons 0.056 |
| Overall | ||
| CADD | 4.102 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.099%
Middle Eastern · 6/6,058 alleles
Filtering AF
0.0546%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0486%
Overall
0.00726%
117/1,612,682 alleles · ultra-rare
exomes 99/1,460,336 · genomes 18/152,346 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.099% | 1,010 |
| Admixed American | 0.0716% | 1,396 |
| South Asian | 0.0428% | 2,335 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,245 |
| African / African-American | 0.00267% | 37,516 |
| European (non-Finnish) | 0.00144% | 69,347 |
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.Lys78=
- Coding
- c.234A>G
- MANE Select
- NM_001031679
- dbSNP
- rs143333399
- Type
- single nucleotide variant
- Location
- chr12:65328574 (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 78
- the msrb domain
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-lys78 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown