Is GDF3 p.Ser232= (c.696C>A) pathogenic?

GDF3 p.Ser232= (c.696C>A) is classified Likely benign in GDF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-09). Very rare (popmax 0.0011%, sas); Associated with GDF3-related disorder.

What condition is associated with GDF3 p.Ser232= (c.696C>A)?

GDF3 p.Ser232= (c.696C>A) is associated with GDF3-related disorder (ClinVar).

How common is GDF3 p.Ser232= (c.696C>A) in the general population?

GDF3 p.Ser232= (c.696C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

GDF3 p.Ser232=

c.696C>A · rs1478637864 · VCV3056871

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

GDF3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.24	phastCons 0.95
Overall
CADD	2.535	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,012 alleles · very rare exomes 9/1,461,888 · genomes 2/152,124 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,082
European (non-Finnish)	0.000847%	118,003

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.Ser232=
Coding: c.696C>A
MANE Select: NM_020634
dbSNP: rs1478637864
Type: single nucleotide variant
Location: chr12:7690277 (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

Disease context

GDF3-related disorder

Similar variants

GDF3 c.268+1G>A Uncertain significance ★ same condition
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

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-ser232 (accessed [today's date]).

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