ACVRL1 p.Pro30=
c.90G>A · rs373401329 · VCV1561065
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0223%, mid)
Conditions
2
Cardiovascular phenotype
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 -4.8 | GERP -4.6 |
| Overall | ||
| CADD | 9.528 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0223%
Middle Eastern · 1/4,480 alleles
Filtering AF
0.00212%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00138%
Overall
0.00131%
21/1,605,912 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0223% | 4,480 |
| South Asian | 0.00555% | 18,014 |
| African / African-American | 0.00535% | 18,707 |
| Admixed American | 0.00504% | 19,840 |
| Finnishnot grpmax-eligible | 0.0033% | 30,338 |
| East Asian | 0.00223% | 44,770 |
| European (non-Finnish) | 0.000424% | 235,805 |
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
- ACVRL1
- Protein
- p.Pro30=
- Coding
- c.90G>A
- MANE Select
- NM_000020
- dbSNP
- rs373401329
- Type
- single nucleotide variant
- Location
- chr12:51913127 (GRCh38)
- Gene constraint
- LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.77 · 7 PDB
- Residue 30
- a UniProt-annotated variant site (in)
Similar variants
- ACVRL1 p.Pro30Ser Likely benign ★★★ same residue
- ACVRL1 p.Pro30fs Pathogenic ★ same residue
- ACVRL1 p.Arg411Gln Pathogenic ★★★ same condition
- ACVRL1 p.Asn98Ser Likely pathogenic ★★★ ⚠ same condition
- ACVRL1 p.Cys46Ser Likely pathogenic ★★★ same condition
- ACVRL1 p.Cys51Gly Likely pathogenic ★★★ same condition
- ACVRL1 p.Cys89Phe Likely pathogenic ★★★ same condition
- ACVRL1 p.Gln490Ter Pathogenic ★★★ same condition
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/acvrl1-p-pro30 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown