MSX2 p.Pro241=
c.723G>A · rs201103544 · VCV697825
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.233%, amr)
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 -1.9 | GERP -4.2 |
| Overall | ||
| CADD | 7.163 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.233%
Admixed American · 140/60,004 alleles
Filtering AF
0.202%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.19%
Overall
0.011%
178/1,613,894 alleles · rare
exomes 169/1,461,618 · genomes 9/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.233% | 429 |
| Middle Eastern | 0.0826% | 1,211 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,623 |
| European (non-Finnish) | 0.00229% | 43,699 |
| African / African-American | 0.00133% | 75,030 |
| South Asian | 0.0011% | 91,070 |
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.Pro241=
- Coding
- c.723G>A
- MANE Select
- NM_002449
- dbSNP
- rs201103544
- Type
- single nucleotide variant
- Location
- chr5:174729502 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 68.77
Similar variants
- MSX2 p.Pro241Leu Uncertain significance ★★ ⚠ same residue
- MSX2 p.Pro241Ala Uncertain significance ★ ⚠ same residue
- MSX2 p.Pro241Arg Uncertain significance ★ same residue
- 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
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-pro241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown