Is GDF2 p.Pro162Thr (c.484C>A) pathogenic?

GDF2 p.Pro162Thr (c.484C>A) is classified Conflicting classifications of pathogenicity in GDF2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.0582); Very rare (popmax 0.00441%, nfe); Associated with telangiectasia, hereditary hemorrhagic, type 5.

What condition is associated with GDF2 p.Pro162Thr (c.484C>A)?

GDF2 p.Pro162Thr (c.484C>A) is associated with telangiectasia, hereditary hemorrhagic, type 5 (ClinVar).

How common is GDF2 p.Pro162Thr (c.484C>A) in the general population?

GDF2 p.Pro162Thr (c.484C>A) is very rare (popmax 0.00441%, nfe) (gnomAD).

How is Hereditary hemorrhagic telangiectasia inherited?

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

What do computational predictors say about GDF2 p.Pro162Thr (c.484C>A)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

GDF2 p.Pro162Thr

c.484C>A · rs139154868 · VCV1342888

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

telangiectasia, hereditary hemorrhagic, type 5

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
SaProt	LLR -6.40	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 -5.5	GERP -5.7
Regional constraint	o/e 0.94	unconstrained · MANE · 3,112 bp · p 0.16 · regional, not allelic
Overall
CADD	0.001	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 0.00441% European (non-Finnish) · 52/1,179,990 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00372% 60/1,613,960 alleles · very rare exomes 53/1,461,760 · genomes 7/152,200 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
European (non-Finnish)grpmax	0.00441%	22,692
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00313%	31,992
Admixed American	0.00167%	60,002

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro162Thr
Coding: c.484C>A
MANE Select: NM_016204
dbSNP: rs139154868
Type: single nucleotide variant
Location: chr10:47324978 (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.Pro162= 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-pro162thr (accessed [today's date]).

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