Is GDF1 p.Ser115= (c.345G>A) pathogenic?

GDF1 p.Ser115= (c.345G>A) is classified Likely benign in GDF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-31). Rare (popmax 0.183%, mid).

How common is GDF1 p.Ser115= (c.345G>A) in the general population?

GDF1 p.Ser115= (c.345G>A) is rare (popmax 0.183%, mid) (gnomAD).

GDF1 p.Ser115=

c.345G>A · rs771475316 · VCV2741290

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.183%, mid)

⚠ 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 -0.96	GERP -2.6
Overall
CADD	7.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.183% Middle Eastern · 8/4,366 alleles

Filtering AF 0.0911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0665%

Overall 0.00523% 80/1,529,956 alleles · rare exomes 74/1,378,050 · genomes 6/151,906 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.183%	546
Admixed American	0.0177%	5,657
East Asian	0.0174%	5,753
Remaining individualsnot grpmax-eligible	0.0101%	9,933
European (non-Finnish)	0.00419%	23,861
African / African-American	0.00277%	36,135

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.Ser115=
Coding: c.345G>A
MANE Select: NM_001492
dbSNP: rs771475316
Type: single nucleotide variant
Location: chr19:18869371 (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-ser115 (accessed [today's date]).

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