Is GDF2 p.Asp218= (c.654C>T) pathogenic?

GDF2 p.Asp218= (c.654C>T) is classified Likely benign in GDF2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-17). Very rare (popmax 0.00678%, nfe); Associated with telangiectasia, hereditary hemorrhagic, type 5.

What condition is associated with GDF2 p.Asp218= (c.654C>T)?

GDF2 p.Asp218= (c.654C>T) is associated with telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Asp218= (c.654C>T) in the general population?

GDF2 p.Asp218= (c.654C>T) is very rare (popmax 0.00678%, nfe) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

GDF2 p.Asp218=

c.654C>T · rs782545137 · VCV1093666

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

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 -0.15	GERP -0.35, phastCons 0.012
Overall
CADD	2.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00678% European (non-Finnish) · 80/1,180,048 alleles

Filtering AF 0.00554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00521% 84/1,613,790 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,751
Remaining individualsnot grpmax-eligible	0.0048%	20,827
African / African-American	0.00133%	74,938

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.Asp218=
Coding: c.654C>T
MANE Select: NM_016204
dbSNP: rs782545137
Type: single nucleotide variant
Location: chr10:47325148 (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.Asp218Asn Benign/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
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-asp218 (accessed [today's date]).

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