Is GDF6 p.Pro204= (c.612G>A) pathogenic?

GDF6 p.Pro204= (c.612G>A) is classified Likely benign in GDF6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-05). Very rare (popmax 0.000174%, nfe); Associated with Leber congenital amaurosis 17.

What condition is associated with GDF6 p.Pro204= (c.612G>A)?

GDF6 p.Pro204= (c.612G>A) is associated with Leber congenital amaurosis 17, Klippel-Feil syndrome 1, autosomal dominant, isolated microphthalmia 4 (ClinVar).

How common is GDF6 p.Pro204= (c.612G>A) in the general population?

GDF6 p.Pro204= (c.612G>A) is very rare (popmax 0.000174%, nfe) (gnomAD).

How is Leber congenital amaurosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GDF6 p.Pro204=

c.612G>A · rs777541984 · VCV1562123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000174%, nfe)

Conditions

Leber congenital amaurosis 17

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 1.2	GERP -2.2, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000174% European (non-Finnish) · 2/1,146,186 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000145% 2/1,381,300 alleles · very rare

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.Pro204=
Coding: c.612G>A
MANE Select: NM_001001557
dbSNP: rs777541984
Type: single nucleotide variant
Location: chr8:96145319 (GRCh38)
Gene constraint: LOEUF 0.342 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.88

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

Disease context

Leber congenital amaurosis 17 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Klippel-Feil syndrome 1, autosomal dominant isolated microphthalmia 4 microphthalmia, isolated, with coloboma 6

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

GDF6 p.Pro204Arg Uncertain significance ★★ ⚠ same residue
GDF6 p.Pro204Gln Uncertain significance ★ ⚠ same residue
GDF6 p.Pro204Leu 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

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-pro204 (accessed [today's date]).

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