Is GDF1 p.Pro57= (c.171G>C) pathogenic?

GDF1 p.Pro57= (c.171G>C) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Very rare (popmax 0.00365%, amr).

How common is GDF1 p.Pro57= (c.171G>C) in the general population?

GDF1 p.Pro57= (c.171G>C) is very rare (popmax 0.00365%, amr) (gnomAD).

GDF1 p.Pro57=

c.171G>C · rs968287517 · VCV2969420

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00365%, 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 -2.7	GERP -2.1
Overall
CADD	1.147	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00365% Admixed American · 2/54,848 alleles

Filtering AF 0.000605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000226%

Overall 0.000128% 2/1,564,512 alleles · very rare exomes 2/1,412,238 · genomes 0/152,274 · 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.Pro57=
Coding: c.171G>C
MANE Select: NM_001492
dbSNP: rs968287517
Type: single nucleotide variant
Location: chr19:18870137 (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-pro57 (accessed [today's date]).

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