Is GDF1 p.Pro159= (c.477G>A) pathogenic?

GDF1 p.Pro159= (c.477G>A) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Very rare (popmax 0.00905%, amr).

How common is GDF1 p.Pro159= (c.477G>A) in the general population?

GDF1 p.Pro159= (c.477G>A) is very rare (popmax 0.00905%, amr) (gnomAD).

GDF1 p.Pro159=

c.477G>A · VCV4805967

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00905%, amr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.5	GERP -2.6
Overall
CADD	7.134	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00905% Admixed American · 3/33,154 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.000353% 5/1,418,048 alleles · very rare exomes 4/1,267,732 · genomes 1/150,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00905%	11,051
European (non-Finnish)	0.000182%	548,598

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.Pro159=
Coding: c.477G>A
MANE Select: NM_001492
Type: single nucleotide variant
Location: chr19:18869239 (GRCh38)

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

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-pro159 (accessed [today's date]).

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