ACVR1 p.Val214=
c.642C>T · rs1393779648 · VCV3021443
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.70 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -5.5 |
| Overall | ||
| CADD | 0.724 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
South Asian · 30/91,038 alleles
Filtering AF
0.0237%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0205%
Overall
0.00341%
55/1,612,836 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.033% | 3,035 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,221 |
| African / African-American | 0.00267% | 37,415 |
| European (non-Finnish) | 0.0017% | 58,956 |
| Admixed American | 0.00167% | 59,982 |
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.Val214=
- Coding
- c.642C>T
- MANE Select
- NM_001111067
- dbSNP
- rs1393779648
- Type
- single nucleotide variant
- Location
- chr2:157774089 (GRCh38)
- Gene constraint
- LOEUF 0.835 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.70 · 85 PDB
- Residue 214
- a β-strand; the protein kinase domain; a binding site
Similar variants
- 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
- ACVR1 p.Arg307Gln Uncertain significance ★★ ⚠ same type
- ACVR1 p.Arg417Gln 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-val214 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown