Is GDF1 p.Pro138= (c.414C>T) pathogenic?

GDF1 p.Pro138= (c.414C>T) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). Ultra-rare (popmax 0.0143%, afr).

How common is GDF1 p.Pro138= (c.414C>T) in the general population?

GDF1 p.Pro138= (c.414C>T) is ultra-rare (popmax 0.0143%, afr) (gnomAD).

GDF1 p.Pro138=

c.414C>T · VCV4749156

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, afr)

⚠ 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 -0.53	GERP -2.5
Overall
CADD	4.704	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% African / African-American · 10/70,108 alleles

Filtering AF 0.00769% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00583%

Overall 0.00336% 51/1,516,458 alleles · ultra-rare exomes 38/1,364,816 · genomes 13/151,642 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0143%	7,011
Admixed American	0.00604%	16,569
Remaining individualsnot grpmax-eligible	0.00508%	19,667
European (non-Finnish)	0.00307%	32,563

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.Pro138=
Coding: c.414C>T
MANE Select: NM_001492
Type: single nucleotide variant
Location: chr19:18869302 (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-pro138 (accessed [today's date]).

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