ACVR1 p.Pro19=
c.57T>C · VCV4751570
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0824%, mid)
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 -3.1 | GERP -5.2 |
| Overall | ||
| CADD | 2.19 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0824%
Middle Eastern · 5/6,070 alleles
Filtering AF
0.0324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.000807%
13/1,611,166 alleles · ultra-rare
exomes 12/1,459,146 · genomes 1/152,020 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0824% | 1,214 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,470 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,560 |
| European (non-Finnish) | 0.00017% | 588,887 |
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.Pro19=
- Coding
- c.57T>C
- MANE Select
- NM_001111067
- Type
- single nucleotide variant
- Location
- chr2:157799437 (GRCh38)
- Gene constraint
- LOEUF 0.835 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.70 · 85 PDB
Similar variants
- ACVR1 p.Pro19Ala Uncertain significance ★ ⚠ same residue
- ACVR1 p.Pro19Leu Uncertain significance ★ ⚠ same residue
- ACVR1 p.Pro19Ser 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
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-pro19 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown