Is GDF6 p.Pro85= (c.255G>T) pathogenic?

GDF6 p.Pro85= (c.255G>T) is classified Benign/Likely benign in GDF6 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.22%, afr); Associated with Leber congenital amaurosis 17.

What condition is associated with GDF6 p.Pro85= (c.255G>T)?

GDF6 p.Pro85= (c.255G>T) is associated with Leber congenital amaurosis 17, Klippel-Feil syndrome 1, autosomal dominant, isolated microphthalmia 4 (ClinVar).

How common is GDF6 p.Pro85= (c.255G>T) in the general population?

GDF6 p.Pro85= (c.255G>T) is low-frequency (popmax 1.22%, afr) (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.Pro85=

c.255G>T · rs112296824 · VCV256847

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, afr)

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	GERP -2.8
Overall
CADD	4.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.22% African / African-American · 916/75,056 alleles

Filtering AF 1.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.13%

Overall 0.0752% 1,213/1,613,862 alleles · low-frequency exomes 691/1,461,544 · genomes 522/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.22%	82
East Asian	0.352%	284
Remaining individualsnot grpmax-eligible	0.11%	906
Admixed American	0.0883%	1,133
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0011%	90,759
South Asian	0.0011%	91,078

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.Pro85=
Coding: c.255G>T
MANE Select: NM_001001557
dbSNP: rs112296824
Type: single nucleotide variant
Location: chr8:96160438 (GRCh38)
Gene constraint: LOEUF 0.342 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.88
Residue 85: the 'disordered' region

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 multiple synostoses syndrome 4

For Leber congenital amaurosis (Orphanet):

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

Similar variants

GDF6 p.Pro85Ser 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-pro85 (accessed [today's date]).

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