Is PDE6D p.Cys86fs (c.257del) pathogenic?

PDE6D p.Cys86fs (c.257del) is classified Likely pathogenic in PDE6D (ClinVar, Single submitter, 2 submitters; last evaluated 2022-04-05). Absent from gnomAD; Associated with Joubert syndrome 22.

What condition is associated with PDE6D p.Cys86fs (c.257del)?

PDE6D p.Cys86fs (c.257del) is associated with Joubert syndrome 22 (ClinVar).

How common is PDE6D p.Cys86fs (c.257del) in the general population?

PDE6D p.Cys86fs (c.257del) is absent from gnomAD (gnomAD).

PDE6D p.Cys86fs

c.257del · rs2048717087 · VCV917951

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Joubert syndrome 22

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 0.67, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDE6D
Protein: p.Cys86fs
Coding: c.257del
MANE Select: NM_002601
dbSNP: rs2048717087
Type: Deletion
Location: chr2:231738021 (GRCh38)
Gene constraint: LOEUF 1.027 · pLI 0.23 (gnomAD)
Structure: AlphaFold pLDDT 96.40 · 40 PDB
Residue 86: a β-strand

Full PDE6D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Joubert syndrome 22 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDE6D p.Cys86= Likely benign ★★ same residue
PDE6D p.Arg23fs Pathogenic ★ same condition
PDE6D p.Glu114fs Pathogenic ★ same condition
PDE6D p.Ser39fs Pathogenic ★ same condition
PDE6D c.51-19del Likely benign ★ same condition
PDE6D p.Arg23Trp Uncertain significance ★★ ⚠ same condition
PDE6D p.Arg75His Uncertain significance ★★ ⚠ same condition
PDE6D c.140-3C>T Likely benign ★★ 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/pde6d-p-cys86fs (accessed [today's date]).

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