Is PDE6B p.Asn643fs (c.1927_1967del) pathogenic?

PDE6B p.Asn643fs (c.19271967del) is classified Pathogenic/Likely pathogenic in PDE6B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-03-01). Absent from gnomAD; Associated with inherited retinal dystrophy.

What condition is associated with PDE6B p.Asn643fs (c.1927_1967del)?

PDE6B p.Asn643fs (c.1927_1967del) is associated with inherited retinal dystrophy, retinitis pigmentosa 40 (ClinVar).

How common is PDE6B p.Asn643fs (c.1927_1967del) in the general population?

PDE6B p.Asn643fs (c.1927_1967del) is absent from gnomAD (gnomAD).

PDE6B p.Asn643fs

c.1927_1967del · rs1296042817 · VCV1184488

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

inherited retinal dystrophy

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 16 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -0.28, 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: PDE6B
Protein: p.Asn643fs
Coding: c.1927_1967del
MANE Select: NM_000283
dbSNP: rs1296042817
Type: Deletion
Location: chr4:663776 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 643: the pdease domain

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

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 40

Similar variants

PDE6B p.Ala143fs 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.Phe95del Uncertain significance ★★ same condition
PDE6B c.1401+4_1401+48del Benign ★★ same condition
PDE6B c.1921-20_1921-3del Likely pathogenic ★ same condition
PDE6B p.Asp279fs 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/pde6b-p-asn643fs (accessed [today's date]).

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