Is GDF2 p.Ser169= (c.507C>T) pathogenic?

GDF2 p.Ser169= (c.507C>T) is classified Likely benign in GDF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-07). Ultra-rare (popmax 0.0156%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GDF2 p.Ser169= (c.507C>T)?

GDF2 p.Ser169= (c.507C>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Ser169= (c.507C>T) in the general population?

GDF2 p.Ser169= (c.507C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

GDF2 p.Ser169=

c.507C>T · rs373090748 · VCV698646

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

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 1.4	GERP -1.6, phastCons 0.59
Overall
CADD	8.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,894 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00661%

Overall 0.00285% 46/1,614,028 alleles · ultra-rare exomes 45/1,461,824 · genomes 1/152,204 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
South Asian	0.0143%	7,006
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00195%	51,305

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.Ser169=
Coding: c.507C>T
MANE Select: NM_016204
dbSNP: rs373090748
Type: single nucleotide variant
Location: chr10:47325001 (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.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-ser169 (accessed [today's date]).

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