Is GDF2 p.Ser73fs (c.217_220del) pathogenic?

GDF2 p.Ser73fs (c.217220del) is classified Pathogenic in GDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-09). Associated with telangiectasia, hereditary hemorrhagic, type 5.

What condition is associated with GDF2 p.Ser73fs (c.217_220del)?

GDF2 p.Ser73fs (c.217_220del) is associated with telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How is Hereditary hemorrhagic telangiectasia inherited?

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

GDF2 p.Ser73fs

c.217_220del · VCV4714707

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

telangiectasia, hereditary hemorrhagic, type 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -1.4, phastCons 1

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

Variant & gene context

Gene: GDF2
Protein: p.Ser73fs
Coding: c.217_220del
MANE Select: NM_016204
Type: Deletion
Location: chr10:47322883 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.79 · 20 PDB

Full GDF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

telangiectasia, hereditary hemorrhagic, type 5 — 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

GDF2 p.Leu251fs Pathogenic ★ same condition
GDF2 p.Leu414fs Pathogenic ★ same condition
GDF2 p.Leu379fs Conflicting classifications of pathogenicity ★ same condition
GDF2 p.Met275fs Conflicting classifications of pathogenicity ★ same condition
GDF2 p.Ser73= Likely benign ★ same residue
GDF2 p.Arg110Gln Likely pathogenic ★★ same condition
GDF2 p.Gln26Ter Pathogenic ★★ same condition
GDF2 p.Glu355Ter 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/gdf2-p-ser73fs (accessed [today's date]).

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