ACVR1 p.Pro9=
c.27T>C · rs368327202 · VCV749595
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00356%, 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 -0.089 | GERP -4.9, phastCons 0.006 |
| Overall | ||
| CADD | 7.283 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
European (non-Finnish) · 42/1,178,854 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00273%
44/1,612,480 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00356% | 28,068 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,200 |
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
- ACVR1
- Protein
- p.Pro9=
- Coding
- c.27T>C
- MANE Select
- NM_001111067
- dbSNP
- rs368327202
- Type
- single nucleotide variant
- Location
- chr2:157799467 (GRCh38)
- Gene constraint
- LOEUF 0.835 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.70 · 85 PDB
Similar variants
- ACVR1 p.Pro9Ser Uncertain significance ★★ ⚠ same residue
- ACVR1 p.Pro9Leu Uncertain significance ★ same residue
- ACVR1 p.Arg206His Pathogenic ★★ same type
- ACVR1 p.Gly328Glu Pathogenic/Likely pathogenic ★★ same type
- ACVR1 p.Gly356Asp Pathogenic/Likely pathogenic ★★ same type
- ACVR1 p.Ala134Thr Uncertain significance ★★ ⚠ same type
- ACVR1 p.Arg147Gln Uncertain significance ★★ ⚠ same type
- ACVR1 p.Arg160Ter 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/acvr1-p-pro9 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown