Is PDE6C p.Arg809fs (c.2425del) pathogenic?

PDE6C p.Arg809fs (c.2425del) is classified Likely pathogenic in PDE6C (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-22). Very rare (popmax 8.48e-05%, nfe); Associated with PDE6C-related disorder.

What condition is associated with PDE6C p.Arg809fs (c.2425del)?

PDE6C p.Arg809fs (c.2425del) is associated with PDE6C-related disorder (ClinVar).

How common is PDE6C p.Arg809fs (c.2425del) in the general population?

PDE6C p.Arg809fs (c.2425del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PDE6C p.Arg809fs

c.2425del · rs2058673701 · VCV866809

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

PDE6C-related disorder

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 21 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.33, phastCons 1
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,424 alleles

Overall 0.000658% 1/152,074 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: PDE6C
Protein: p.Arg809fs
Coding: c.2425del
MANE Select: NM_006204
dbSNP: rs2058673701
Type: Deletion
Location: chr10:93663085 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.53 · 7 PDB
Residue 809: an α-helix; a UniProt-annotated variant site (in achm5); the pdease domain

Full PDE6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PDE6C-related disorder

Similar variants

PDE6C p.Arg809_Val810insTer Pathogenic ★ same residue
PDE6C c.2367+1_2367+5del Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg769_Asp770insTer Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Ile714fs Likely pathogenic ★ same condition
PDE6C p.Lys488fs Likely pathogenic ★ same condition
PDE6C p.Arg809= Conflicting classifications of pathogenicity ★ same residue
PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.481-1G>A Likely pathogenic ★★ 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/pde6c-p-arg809fs (accessed [today's date]).

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