Is ACVRL1 p.Pro39= (c.117A>G) pathogenic?

ACVRL1 p.Pro39= (c.117A>G) is classified Likely benign in ACVRL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). Absent from gnomAD v4.1; Associated with telangiectasia, hereditary hemorrhagic, type 2.

What condition is associated with ACVRL1 p.Pro39= (c.117A>G)?

ACVRL1 p.Pro39= (c.117A>G) is associated with telangiectasia, hereditary hemorrhagic, type 2 (ClinVar).

How common is ACVRL1 p.Pro39= (c.117A>G) in the general population?

ACVRL1 p.Pro39= (c.117A>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

ACVRL1 p.Pro39=

c.117A>G · VCV4719264

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

telangiectasia, hereditary hemorrhagic, type 2

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 -0.61	GERP -3.7
Overall
CADD	3.564	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ACVRL1
Protein: p.Pro39=
Coding: c.117A>G
MANE Select: NM_000020
Type: single nucleotide variant
Location: chr12:51913154 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.51 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.77 · 7 PDB

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

Disease context

telangiectasia, hereditary hemorrhagic, type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary hemorrhagic telangiectasia (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

ACVRL1 p.Pro39fs 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-pro39 (accessed [today's date]).

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