ACVRL1 p.Pro368=
c.1104G>A · rs147885255 · VCV695778
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0535%, eas)
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 -7.8 | GERP -5 |
| Overall | ||
| CADD | 4.409 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0535%
East Asian · 24/44,852 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0313%
Overall
0.00762%
123/1,613,380 alleles · ultra-rare
exomes 116/1,461,190 · genomes 7/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0535% | 1,869 |
| European (non-Finnish) | 0.0078% | 12,821 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,608 |
| Admixed American | 0.005% | 19,999 |
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.Pro368=
- Coding
- c.1104G>A
- MANE Select
- NM_000020
- dbSNP
- rs147885255
- Type
- single nucleotide variant
- Location
- chr12:51916091 (GRCh38)
- Gene constraint
- LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.77 · 7 PDB
- Residue 368
- the protein kinase domain
Similar variants
- ACVRL1 p.Pro368Leu Uncertain significance ★★ ⚠ 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
- ACVRL1 p.Glu236Lys 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-pro368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown