Is PDE6B p.Phe95del (c.283_285del) pathogenic?

PDE6B p.Phe95del (c.283285del) is classified Uncertain significance in PDE6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-23). Very rare (popmax 0.00111%, sas); Associated with retinitis pigmentosa 40.

What condition is associated with PDE6B p.Phe95del (c.283_285del)?

PDE6B p.Phe95del (c.283_285del) is associated with retinitis pigmentosa 40 (ClinVar).

How common is PDE6B p.Phe95del (c.283_285del) in the general population?

PDE6B p.Phe95del (c.283_285del) is very rare (popmax 0.00111%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6B p.Phe95del

c.283_285del · VCV4854842

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

retinitis pigmentosa 40

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.6	GERP 2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/89,786 alleles

Overall 0.000138% 2/1,451,428 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00161%	62,078
South Asiangrpmax	0.00111%	89,786

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe95del
Coding: c.283_285del
MANE Select: NM_000283
Type: Deletion
Location: chr4:625907 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 95: the gaf 1 domain

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

Disease context

retinitis pigmentosa 40 — 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

PDE6B p.Asn643fs Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.His620fs Pathogenic ★★ same condition
PDE6B p.Leu514fs Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Thr497fs Pathogenic ★★ same condition
PDE6B p.Asp279fs Likely pathogenic ★ same condition
PDE6B p.Glu822fs Pathogenic ★ same condition
PDE6B c.2353-7_2353-3del Uncertain significance ★ same condition
PDE6B p.Phe95= Conflicting classifications of pathogenicity ★ same residue

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-phe95del (accessed [today's date]).

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