ACVR1 p.Thr249=
c.747G>A · rs775087563 · VCV2177067
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, afr)
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 1.2 | GERP -0.74, phastCons 1 |
| Overall | ||
| CADD | 12.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
African / African-American · 13/74,878 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00813%
Overall
0.00173%
28/1,613,922 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0174% | 5,760 |
| South Asian | 0.00439% | 22,772 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.000847% | 117,997 |
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.Thr249=
- Coding
- c.747G>A
- MANE Select
- NM_001111067
- dbSNP
- rs775087563
- Type
- single nucleotide variant
- Location
- chr2:157770411 (GRCh38)
- Gene constraint
- LOEUF 0.835 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.70 · 85 PDB
- Residue 249
- an α-helix; the protein kinase domain
Similar variants
- ACVR1 p.Thr249Met 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
- ACVR1 p.Arg307Gln 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-thr249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown