Is GDF2 p.Ile339= (c.1017C>T) pathogenic?

GDF2 p.Ile339= (c.1017C>T) is classified Benign/Likely benign in GDF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Rare (popmax 0.187%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with GDF2 p.Ile339= (c.1017C>T)?

GDF2 p.Ile339= (c.1017C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Ile339= (c.1017C>T) in the general population?

GDF2 p.Ile339= (c.1017C>T) is rare (popmax 0.187%, nfe) (gnomAD).

GDF2 p.Ile339=

c.1017C>T · rs148730910 · VCV381779

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.187%, nfe)

Conditions

Cardiovascular phenotype

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 -13	GERP -3.7
Overall
CADD	0.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.187% European (non-Finnish) · 2,209/1,180,034 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.142% 2,286/1,613,846 alleles · rare exomes 2,173/1,461,520 · genomes 113/152,326 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.187%	534
Remaining individualsnot grpmax-eligible	0.0688%	1,454
African / African-American	0.0213%	4,692
Finnishnot grpmax-eligible	0.0126%	7,960
Admixed American	0.01%	10,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
East Asian	0.00223%	44,876
South Asian	0.0022%	45,542

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GDF2
Protein: p.Ile339=
Coding: c.1017C>T
MANE Select: NM_016204
dbSNP: rs148730910
Type: single nucleotide variant
Location: chr10:47325511 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.79 · 20 PDB
Residue 339: a turn

Full GDF2 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 5

Similar variants

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
GDF2 p.Arg30Pro 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-ile339 (accessed [today's date]).

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