Is ACVRL1 p.Pro44fs (c.130_143del) pathogenic?

ACVRL1 p.Pro44fs (c.130143del) is classified Pathogenic in ACVRL1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-10). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with ACVRL1 p.Pro44fs (c.130_143del)?

ACVRL1 p.Pro44fs (c.130_143del) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 2 (ClinVar).

How common is ACVRL1 p.Pro44fs (c.130_143del) in the general population?

ACVRL1 p.Pro44fs (c.130_143del) is absent from gnomAD (gnomAD).

ACVRL1 p.Pro44fs

c.130_143del · rs2139064592 · VCV1359265

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.51	GERP -4.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ACVRL1
Protein: p.Pro44fs
Coding: c.130_143del
MANE Select: NM_000020
dbSNP: rs2139064592
Type: Deletion
Location: chr12:51913163 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 7 PDB
Residue 44: a β-strand; a disulfide bond

Full ACVRL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: telangiectasia, hereditary hemorrhagic, type 2

Similar variants

ACVRL1 p.Cys207fs Pathogenic ★★★ same condition
ACVRL1 p.Glu148del Uncertain significance ★★★ same condition
ACVRL1 c.525+1del Pathogenic ★★ same condition
ACVRL1 p.Ala400fs Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 p.Asp254del Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 p.Gln343_Leu349del Pathogenic/Likely pathogenic ★★ same condition
ACVRL1 p.Glu65fs Pathogenic ★★ same condition
ACVRL1 p.Gly136fs Pathogenic/Likely 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-pro44fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown