Is GDF1 p.Pro33fs (c.98del) pathogenic?

GDF1 p.Pro33fs (c.98del) is classified Likely pathogenic in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-15). Very rare (popmax 0.00231%, eas); Associated with GDF1-RELATED DISORDERS.

What condition is associated with GDF1 p.Pro33fs (c.98del)?

GDF1 p.Pro33fs (c.98del) is associated with GDF1-RELATED DISORDERS (ClinVar).

How common is GDF1 p.Pro33fs (c.98del) in the general population?

GDF1 p.Pro33fs (c.98del) is very rare (popmax 0.00231%, eas) (gnomAD).

GDF1 p.Pro33fs

c.98del · VCV4941674

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

Conditions

GDF1-RELATED DISORDERS

⚠ 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.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.4	GERP -2.4
Region caveats
Repeat context	tandem	G-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% East Asian · 1/43,248 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.000642% 10/1,557,722 alleles · very rare exomes 10/1,406,010 · genomes 0/151,712 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0033%	30,325
East Asiangrpmax	0.00231%	43,248
South Asian	0.00118%	85,066
European (non-Finnish)	0.000518%	193,019

Remaining individuals 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.Pro33fs
Coding: c.98del
MANE Select: NM_001492
Type: Deletion
Location: chr19:18870210 (GRCh38)

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

Disease context

GDF1-RELATED DISORDERS

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-pro33fs (accessed [today's date]).

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