Is GDF2 p.Ser402= (c.1206C>T) pathogenic?

GDF2 p.Ser402= (c.1206C>T) is classified Likely benign in GDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-29). Ultra-rare (popmax 0.0166%, mid); Associated with Cardiovascular phenotype.

What condition is associated with GDF2 p.Ser402= (c.1206C>T)?

GDF2 p.Ser402= (c.1206C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is GDF2 p.Ser402= (c.1206C>T) in the general population?

GDF2 p.Ser402= (c.1206C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

GDF2 p.Ser402=

c.1206C>T · rs782104232 · VCV1748823

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

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 -2	GERP -3.7
Overall
CADD	8.946	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0166% Middle Eastern · 1/6,024 alleles

Filtering AF 0.00445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00131% 21/1,602,528 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,024
South Asian	0.00898%	11,139
African / African-American	0.00535%	18,691
Remaining individualsnot grpmax-eligible	0.00161%	61,996
European (non-Finnish)	0.000597%	167,623

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.Ser402=
Coding: c.1206C>T
MANE Select: NM_016204
dbSNP: rs782104232
Type: single nucleotide variant
Location: chr10:47325700 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 75.79 · 20 PDB
Residue 402: a disulfide bond; a β-strand; the 'interaction with eng' region

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

Similar variants

GDF2 p.Ala105Gly Uncertain significance ★★ ⚠ same condition
GDF2 p.Arg333Gln Uncertain significance ★★ ⚠ same condition
GDF2 p.Gly247Val Uncertain significance ★★ ⚠ same condition
GDF2 p.Ala105= Likely benign ★★ same condition
GDF2 p.Ala310= Likely benign ★★ same condition
GDF2 p.Ala365= Likely benign ★★ same condition
GDF2 p.Arg319= Likely benign ★★ same condition
GDF2 p.Asn259Ser Benign/Likely benign ★★ 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-ser402 (accessed [today's date]).

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