ACVR1 p.Pro465=
c.1395G>A · rs373855918 · VCV3006873
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
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 |
|---|---|---|
| Pangolin | Δ0.23 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.24 | GERP -2.4, phastCons 0.98 |
| Overall | ||
| CADD | 18.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,898 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000744%
12/1,613,910 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,449 |
| Admixed American | 0.00333% | 30,000 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| African / African-American | 0.00133% | 74,912 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000339% | 294,983 |
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.Pro465=
- Coding
- c.1395G>A
- MANE Select
- NM_001111067
- dbSNP
- rs373855918
- Type
- single nucleotide variant
- Location
- chr2:157738440 (GRCh38)
- Gene constraint
- LOEUF 0.835 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.70 · 85 PDB
- Residue 465
- the protein kinase domain; an α-helix
Similar variants
- ACVR1 p.Pro465Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- ACVR1 p.Pro465Ser 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-pro465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown