ACVRL1 p.Phe331=
c.993C>T · rs56379428 · VCV515939
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.307%, 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 1.5 | GERP -0.95, phastCons 1 |
| Overall | ||
| CADD | 12.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.307%
East Asian · 138/44,886 alleles
Filtering AF
0.266%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.25%
Overall
0.00948%
153/1,613,540 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.307% | 325 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,206 |
| South Asian | 0.0022% | 45,541 |
| Admixed American | 0.00167% | 60,034 |
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.Phe331=
- Coding
- c.993C>T
- MANE Select
- NM_000020
- dbSNP
- rs56379428
- Type
- single nucleotide variant
- Location
- chr12:51915445 (GRCh38)
- Gene constraint
- LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.77 · 7 PDB
- Residue 331
- the protein kinase domain
Similar variants
- ACVRL1 p.Phe331Ser 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
- 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-phe331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown