Is GDF3 p.Pro39Ser (c.115C>T) pathogenic?

GDF3 p.Pro39Ser (c.115C>T) is classified Uncertain significance in GDF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.2617); Very rare (popmax 6.2e-05%).

How common is GDF3 p.Pro39Ser (c.115C>T) in the general population?

GDF3 p.Pro39Ser (c.115C>T) is very rare (popmax 6.2e-05%) (gnomAD).

What do computational predictors say about GDF3 p.Pro39Ser (c.115C>T)?

AlphaMissense predicts likely benign (score 0.2617) — an in-silico prediction, not a clinical call.

GDF3 p.Pro39Ser

c.115C>T · VCV4262774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2617 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2617	likely benign
REVEL	0.444	indeterminate
SaProt	LLR -12.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 5,847 bp · p 0.58 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,614,132 alleles · very rare exomes 1/1,461,864 · genomes 0/152,268 · 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: GDF3
Protein: p.Pro39Ser
Coding: c.115C>T
MANE Select: NM_020634
Type: single nucleotide variant
Location: chr12:7695614 (GRCh38)
Gene constraint: LOEUF 1.513 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.72

Full GDF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

GDF3 p.Arg274Trp Uncertain significance ★★ ⚠ same type
GDF3 p.Pro325Thr Uncertain significance ★★ ⚠ same type
GDF3 p.Ser304Pro Uncertain significance ★★ ⚠ same type
GDF3 p.Val320Ile Uncertain significance ★★ ⚠ same type
GDF3 c.268+117G>A Benign ★★ same type
GDF3 c.269-73G>A Benign ★★ same type
GDF3 p.Arg195Trp Benign/Likely benign ★★ same type
GDF3 p.Asn193= Benign/Likely benign ★★ same type

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/gdf3-p-pro39ser (accessed [today's date]).

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