Is GDF1 p.Pro53= (c.159C>T) pathogenic?

GDF1 p.Pro53= (c.159C>T) is classified Benign/Likely benign in GDF1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-27). Ultra-rare (popmax 0.0695%, mid).

How common is GDF1 p.Pro53= (c.159C>T) in the general population?

GDF1 p.Pro53= (c.159C>T) is ultra-rare (popmax 0.0695%, mid) (gnomAD).

GDF1 p.Pro53=

c.159C>T · rs755093676 · VCV539308

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0695%, mid)

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 -0.16	GERP -1.8
Overall
CADD	6.112	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0695% Middle Eastern · 4/5,754 alleles

Filtering AF 0.0312% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.00864% 135/1,562,656 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0991%	1,009
Middle Easterngrpmax	0.0695%	1,438
African / African-American	0.043%	2,328
Remaining individualsnot grpmax-eligible	0.0428%	2,336
Admixed American	0.00732%	13,653
European (non-Finnish)	0.00345%	28,992
South Asian	0.00117%	85,616

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: GDF1
Protein: p.Pro53=
Coding: c.159C>T
MANE Select: NM_021267 · reported on NM_001492
dbSNP: rs755093676
Type: single nucleotide variant
Location: chr19:18870149 (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-pro53 (accessed [today's date]).

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