Is GDF2 p.Ile118Phe (c.352A>T) pathogenic?

GDF2 p.Ile118Phe (c.352A>T) is classified Benign/Likely benign in GDF2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.0851); Rare (popmax 0.908%, eas); Associated with Cardiovascular phenotype.

What condition is associated with GDF2 p.Ile118Phe (c.352A>T)?

GDF2 p.Ile118Phe (c.352A>T) is associated with Cardiovascular phenotype, telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Ile118Phe (c.352A>T) in the general population?

GDF2 p.Ile118Phe (c.352A>T) is rare (popmax 0.908%, eas) (gnomAD).

What do computational predictors say about GDF2 p.Ile118Phe (c.352A>T)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

GDF2 p.Ile118Phe

c.352A>T · rs144456901 · VCV993986

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.908%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
SaProt	LLR -6.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -5.1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,112 bp · p 0.16 · regional, not allelic
Overall
CADD	0.104	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.908% East Asian · 407/44,836 alleles

Filtering AF 0.835% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.806%

Overall 0.0319% 514/1,609,598 alleles · rare exomes 431/1,457,270 · genomes 83/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.908%	110
Remaining individualsnot grpmax-eligible	0.0801%	1,248
South Asian	0.0538%	1,857
Admixed American	0.00167%	60,000
European (non-Finnish)	0.000595%	168,194

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.Ile118Phe
Coding: c.352A>T
MANE Select: NM_016204
dbSNP: rs144456901
Type: single nucleotide variant
Location: chr10:47324846 (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-ile118phe (accessed [today's date]).

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