Is ACVRL1 p.Arg7= (c.21G>A) pathogenic?

ACVRL1 p.Arg7= (c.21G>A) is classified Likely benign in ACVRL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). Absent from gnomAD v4.1; Associated with telangiectasia, hereditary hemorrhagic, type 2.

What condition is associated with ACVRL1 p.Arg7= (c.21G>A)?

ACVRL1 p.Arg7= (c.21G>A) is associated with telangiectasia, hereditary hemorrhagic, type 2 (ClinVar).

How common is ACVRL1 p.Arg7= (c.21G>A) in the general population?

ACVRL1 p.Arg7= (c.21G>A) 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.Arg7=

c.21G>A · VCV3617456

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 0.28	GERP -4.4, phastCons 0.13
Overall
CADD	2.357	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.Arg7=
Coding: c.21G>A
MANE Select: NM_000020
Type: single nucleotide variant
Location: chr12:51912495 (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.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
ACVRL1 p.His328Tyr 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-arg7 (accessed [today's date]).

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