ACVRL1 p.Phe84=
c.252C>T · VCV4916880
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00535%, 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 -5.8 | GERP -4.7 |
| Overall | ||
| CADD | 5.967 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00535%
African / African-American · 4/74,826 alleles
Filtering AF
0.00175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00124%
20/1,608,488 alleles · very rare
exomes 17/1,456,358 · genomes 3/152,130 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00535% | 18,706 |
| Finnishnot grpmax-eligible | 0.00319% | 31,392 |
| European (non-Finnish) | 0.00119% | 84,134 |
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.Phe84=
- Coding
- c.252C>T
- MANE Select
- NM_000020
- Type
- single nucleotide variant
- Location
- chr12:51913289 (GRCh38)
- Gene constraint
- LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.77 · 7 PDB
- Residue 84
- a β-strand
Similar variants
- ACVRL1 p.Phe84Cys Uncertain significance ★ ⚠ same residue
- ACVRL1 p.Arg411Gln Pathogenic ★★★ same type
- ACVRL1 p.Asn98Ser Likely pathogenic ★★★ ⚠ same type
- ACVRL1 p.Cys46Ser Likely pathogenic ★★★ same type
- ACVRL1 p.Cys51Gly Likely pathogenic ★★★ same type
- ACVRL1 p.Cys89Phe Likely pathogenic ★★★ same type
- ACVRL1 p.Gln490Ter Pathogenic ★★★ same type
- ACVRL1 p.Glu236Lys Pathogenic ★★★ 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/acvrl1-p-phe84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown