Is GDF1 p.Pro288= (c.864G>A) pathogenic?

GDF1 p.Pro288= (c.864G>A) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-08). Very rare (popmax 6.91e-05%).

How common is GDF1 p.Pro288= (c.864G>A) in the general population?

GDF1 p.Pro288= (c.864G>A) is very rare (popmax 6.91e-05%) (gnomAD).

GDF1 p.Pro288=

c.864G>A · rs2055903918 · VCV2878553

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.91e-05%)

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 -9.7	GERP -4
Overall
CADD	6.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.91e-05%

Overall 6.91e-05% 1/1,446,688 alleles · very rare exomes 1/1,298,100 · genomes 0/148,588 · 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: GDF1
Protein: p.Pro288=
Coding: c.864G>A
MANE Select: NM_001492
dbSNP: rs2055903918
Type: single nucleotide variant
Location: chr19:18868852 (GRCh38)
Gene constraint: LOEUF 1.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.44
Residue 288: a UniProt-annotated variant site (in chtd6 and rai)

Full GDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CERS1 p.His233Arg Uncertain significance ★★ ⚠ same type
CERS1 p.His236Gln Uncertain significance ★★ same type
CERS1 p.Lys98Arg Uncertain significance ★★ ⚠ same type
CERS1 p.Pro140Leu Uncertain significance ★★ ⚠ same type
CERS1 p.Pro260Leu Uncertain significance ★★ ⚠ same type
CERS1 p.Pro84Thr Uncertain significance ★★ same type
CERS1 p.Ser330Ile Uncertain significance ★★ ⚠ same type
GDF1 p.Arg64Cys Uncertain significance ★★ ⚠ 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/gdf1-p-pro288 (accessed [today's date]).

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