MSX1 p.Arg280=
c.840C>T · VCV4966222
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00399%, nfe)
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 -3.8 |
| Overall | ||
| CADD | 7.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00399%
European (non-Finnish) · 47/1,178,262 alleles
Filtering AF
0.00307%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00275%
Overall
0.00305%
49/1,608,380 alleles · very rare
exomes 45/1,456,176 · genomes 4/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00399% | 25,069 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,162 |
| African / African-American | 0.00134% | 74,754 |
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
- MSX1
- Protein
- p.Arg280=
- Coding
- c.840C>T
- MANE Select
- NM_002448
- Type
- single nucleotide variant
- Location
- chr4:4863071 (GRCh38)
- Gene constraint
- LOEUF 1.289 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 66.06
- Residue 280
- a UniProt-annotated variant site (in ectd3)
Similar variants
- MSX1 p.Ala182Thr Uncertain significance ★★ ⚠ same type
- MSX1 p.Ala261Gly Uncertain significance ★★ ⚠ same type
- MSX1 p.Arg224Cys Uncertain significance ★★ ⚠ same type
- MSX1 p.Glu128Lys Uncertain significance ★★ ⚠ same type
- MSX1 p.Val263Leu Uncertain significance ★★ ⚠ same type
- MSX1 c.470-127C>A Benign ★★ same type
- MSX1 c.470-129G>A Benign ★★ same type
- MSX1 c.470-152A>G Benign ★★ 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/msx1-p-arg280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown