Is GDF2 p.Arg151Ter (c.451C>T) pathogenic?

GDF2 p.Arg151Ter (c.451C>T) is classified Conflicting classifications of pathogenicity in GDF2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-26). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GDF2 p.Arg151Ter (c.451C>T)?

GDF2 p.Arg151Ter (c.451C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Arg151Ter (c.451C>T) in the general population?

GDF2 p.Arg151Ter (c.451C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

GDF2 p.Arg151Ter

c.451C>T · rs782238805 · VCV2609335

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.2	GERP 0.54, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,614,022 alleles · very rare exomes 5/1,461,712 · genomes 0/152,310 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
South Asian	0.0011%	91,074
European (non-Finnish)	0.000254%	393,315

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.Arg151Ter
Coding: c.451C>T
MANE Select: NM_016204
dbSNP: rs782238805
Type: single nucleotide variant
Location: chr10:47324945 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: telangiectasia, hereditary hemorrhagic, type 5

Similar variants

GDF2 p.Arg151= Likely benign ★ same residue
GDF2 p.Arg151Gln 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
GDF2 p.Trp214Ter Pathogenic/Likely pathogenic ★★ same condition
GDF2 p.Val423Met Pathogenic/Likely pathogenic ★★ same condition
GDF2 p.Ala105Gly 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-arg151ter (accessed [today's date]).

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