Is GDF6 p.Ser30= (c.90C>G) pathogenic?

GDF6 p.Ser30= (c.90C>G) is classified Likely benign in GDF6 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-21). Ultra-rare (popmax 0.032%, afr); Associated with Klippel-Feil syndrome 1, autosomal dominant.

What condition is associated with GDF6 p.Ser30= (c.90C>G)?

GDF6 p.Ser30= (c.90C>G) is associated with Klippel-Feil syndrome 1, autosomal dominant, isolated microphthalmia 4, microphthalmia, isolated, with coloboma 6 (ClinVar).

How common is GDF6 p.Ser30= (c.90C>G) in the general population?

GDF6 p.Ser30= (c.90C>G) is ultra-rare (popmax 0.032%, afr) (gnomAD).

GDF6 p.Ser30=

c.90C>G · rs143020575 · VCV794822

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Conditions

Klippel-Feil syndrome 1, autosomal dominant

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 -0.42	GERP -2.5, phastCons 0.001
Overall
CADD	5.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/75,052 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.0018% 29/1,613,736 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00333%	30,009

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: GDF6
Protein: p.Ser30=
Coding: c.90C>G
MANE Select: NM_001001557
dbSNP: rs143020575
Type: single nucleotide variant
Location: chr8:96160603 (GRCh38)
Gene constraint: LOEUF 0.342 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.88
Residue 30: the 'disordered' region

Full GDF6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Klippel-Feil syndrome 1, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: isolated microphthalmia 4 microphthalmia, isolated, with coloboma 6 Leber congenital amaurosis 17

Similar variants

GDF6 p.Ser30Phe Uncertain significance ★ ⚠ same residue
GDF6 c.*268G>C Uncertain significance ★★ same condition
GDF6 c.*273C>T Uncertain significance ★★ same condition
GDF6 c.*274T>C Uncertain significance ★★ same condition
GDF6 p.Ala199Thr Uncertain significance ★★ ⚠ same condition
GDF6 p.Ala199Val Uncertain significance ★★ ⚠ same condition
GDF6 p.Ala242Thr Uncertain significance ★★ ⚠ same condition
GDF6 p.Ala247Glu Uncertain significance ★★ ⚠ same condition

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/gdf6-p-ser30 (accessed [today's date]).

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