Is GDF5 p.Arg402= (c.1204C>A) pathogenic?

GDF5 p.Arg402= (c.1204C>A) is classified Likely benign in GDF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.2896); Very rare (popmax 8.47e-05%, nfe).

How common is GDF5 p.Arg402= (c.1204C>A) in the general population?

GDF5 p.Arg402= (c.1204C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about GDF5 p.Arg402= (c.1204C>A)?

AlphaMissense predicts likely benign (score 0.2896) — an in-silico prediction, not a clinical call.

GDF5 p.Arg402=

c.1204C>A · rs1216891950 · VCV2034956

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2896	likely benign
REVEL	0.477	indeterminate
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.8	GERP -1.2, phastCons 1
Overall
CADD	16.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,014 alleles

Overall 6.2e-05% 1/1,614,164 alleles · very rare exomes 1/1,461,852 · genomes 0/152,312 · joint denominator

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: GDF5
Protein: p.Arg402=
Coding: c.1204C>A
MANE Select: NM_000557
dbSNP: rs1216891950
Type: single nucleotide variant
Location: chr20:35434211 (GRCh38)
Gene constraint: LOEUF 0.71 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 71.04 · 15 PDB
Residue 402: a β-strand

Full GDF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GDF5 p.Arg402Trp Uncertain significance ★ ⚠ same residue
GDF5 p.Arg156Ter Pathogenic/Likely pathogenic ★★ same type
GDF5 p.Arg301Ter Pathogenic/Likely pathogenic ★★ ⚠ same type
GDF5 p.Arg380Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
GDF5 p.Cys400Tyr Likely pathogenic ★★ same type
GDF5 p.Gln210Ter Pathogenic/Likely pathogenic ★★ same type
GDF5 p.Glu491Lys Pathogenic ★★ ⚠ same type
GDF5 p.Trp297Ter Pathogenic/Likely pathogenic ★★ same type

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/gdf5-p-arg402 (accessed [today's date]).

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