Is PDE6B p.Arg82fs (c.243del) pathogenic?

PDE6B p.Arg82fs (c.243del) is classified Pathogenic in PDE6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-06). Very rare (popmax 0.0011%, sas); Associated with PDE6B-related disorder.

What condition is associated with PDE6B p.Arg82fs (c.243del)?

PDE6B p.Arg82fs (c.243del) is associated with PDE6B-related disorder (ClinVar).

How common is PDE6B p.Arg82fs (c.243del) in the general population?

PDE6B p.Arg82fs (c.243del) is very rare (popmax 0.0011%, sas) (gnomAD).

PDE6B p.Arg82fs

c.243del · VCV4747388

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

PDE6B-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 1 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.18	GERP -3.7, phastCons 0.24

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,630 alleles

Overall 6.86e-05% 1/1,457,588 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: PDE6B
Protein: p.Arg82fs
Coding: c.243del
MANE Select: NM_000283
Type: Deletion
Location: chr4:625868 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 82: the gaf 1 domain

Full PDE6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PDE6B-related disorder

Similar variants

PDE6B c.2353-18_2354del Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Asp252fs Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.His620fs Pathogenic ★★ same condition
PDE6B p.Leu27fs Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Leu514fs Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.985_992+21del Likely pathogenic ★ same condition
PDE6B p.Ala733fs Likely pathogenic ★ same condition
PDE6B p.Arg651fs 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/pde6b-p-arg82fs (accessed [today's date]).

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