MSX2 p.Leu76=
c.228G>A · rs999180495 · VCV1615024
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0027%, afr)
Conditions
1
Cranium bifidum occultum
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 1.4 | GERP 0.5, phastCons 1 |
| Overall | ||
| CADD | 11.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0027%
African / African-American · 2/74,182 alleles
Filtering AF
0.000447%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000168%
Overall
0.000128%
2/1,562,696 alleles · very rare
exomes 1/1,410,460 · genomes 1/152,236 · joint denominator
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
- MSX2
- Protein
- p.Leu76=
- Coding
- c.228G>A
- MANE Select
- NM_002449
- dbSNP
- rs999180495
- Type
- single nucleotide variant
- Location
- chr5:174724887 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.77
Similar variants
- MSX2 p.Gln153Ter Pathogenic/Likely pathogenic ★★ same condition
- MSX2 p.Ala212Gly Uncertain significance ★★ ⚠ same condition
- MSX2 p.Ala238Thr Uncertain significance ★★ ⚠ same condition
- MSX2 p.Arg143Gln Uncertain significance ★★ ⚠ same condition
- MSX2 p.Arg39Leu Uncertain significance ★★ ⚠ same condition
- MSX2 p.Arg87Trp Uncertain significance ★★ ⚠ same condition
- MSX2 p.Glu32Val Uncertain significance ★★ ⚠ same condition
- MSX2 p.Gly23Arg Uncertain significance ★★ ⚠ same condition
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/msx2-p-leu76 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown