Is PDE6A p.Asp366fs (c.1097del) pathogenic?

PDE6A p.Asp366fs (c.1097del) is classified Likely pathogenic in PDE6A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-08). Very rare (popmax 8.48e-05%, nfe); Associated with retinitis pigmentosa 43.

What condition is associated with PDE6A p.Asp366fs (c.1097del)?

PDE6A p.Asp366fs (c.1097del) is associated with retinitis pigmentosa 43 (ClinVar).

How common is PDE6A p.Asp366fs (c.1097del) in the general population?

PDE6A p.Asp366fs (c.1097del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6A p.Asp366fs

c.1097del · rs1581186849 · VCV817435

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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

Conditions

retinitis pigmentosa 43

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 8 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.3	GERP -0.31, phastCons 1

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) · 1/1,179,618 alleles

Overall 6.84e-05% 1/1,461,416 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: PDE6A
Protein: p.Asp366fs
Coding: c.1097del
MANE Select: NM_000440
dbSNP: rs1581186849
Type: Deletion
Location: chr5:149903664 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 366: the gaf 2 domain

Full PDE6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 43 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PDE6A p.Asp778fs Pathogenic/Likely pathogenic ★★ same condition
PDE6A p.Gly844fs Uncertain significance ★★ same condition
PDE6A p.Gly850fs Uncertain significance ★★ same condition
PDE6A p.Gln699fs Pathogenic ★ same condition
PDE6A p.Ile453fs Likely pathogenic ★ same condition
PDE6A p.Pro512fs Likely pathogenic ★ same condition
PDE6A p.Asp366Gly Uncertain significance ★ same residue
PDE6A p.Tyr583_Phe584del Conflicting classifications of pathogenicity ★ 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/pde6a-p-asp366fs (accessed [today's date]).

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