Is GDF2 p.Ile139= (c.417T>A) pathogenic?

GDF2 p.Ile139= (c.417T>A) is classified Likely benign in GDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-13). Absent from gnomAD v4.1; Associated with telangiectasia, hereditary hemorrhagic, type 5.

What condition is associated with GDF2 p.Ile139= (c.417T>A)?

GDF2 p.Ile139= (c.417T>A) is associated with telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Ile139= (c.417T>A) in the general population?

GDF2 p.Ile139= (c.417T>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.

GDF2 p.Ile139=

c.417T>A · VCV3659431

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 5

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 -0.54	GERP -5.4, phastCons 0.045
Overall
CADD	6.096	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: GDF2
Protein: p.Ile139=
Coding: c.417T>A
MANE Select: NM_016204
Type: single nucleotide variant
Location: chr10:47324911 (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.Ile139Thr Uncertain significance ★ ⚠ same residue
GDF2 p.Arg110Gln Likely pathogenic ★★ same condition
GDF2 p.Gln26Ter Pathogenic ★★ same condition
GDF2 p.Glu355Ter Pathogenic/Likely pathogenic ★★ same condition
GDF2 p.Trp214Ter Pathogenic/Likely pathogenic ★★ same condition
GDF2 p.Val423Met Pathogenic/Likely pathogenic ★★ same condition
GDF2 p.Ala105Gly Uncertain significance ★★ ⚠ same condition
GDF2 p.Arg213Cys Uncertain significance ★★ ⚠ 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-ile139 (accessed [today's date]).

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