Is PDE6B p.Arg602Ser (c.1804C>A) pathogenic?

PDE6B p.Arg602Ser (c.1804C>A) is classified Uncertain significance in PDE6B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9993); Very rare (popmax 0.00017%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PDE6B p.Arg602Ser (c.1804C>A)?

PDE6B p.Arg602Ser (c.1804C>A) is associated with retinitis pigmentosa, congenital stationary night blindness autosomal dominant 2 (ClinVar).

How common is PDE6B p.Arg602Ser (c.1804C>A) in the general population?

PDE6B p.Arg602Ser (c.1804C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about PDE6B p.Arg602Ser (c.1804C>A)?

AlphaMissense predicts likely pathogenic (score 0.9993) — an in-silico prediction, not a clinical call.

PDE6B p.Arg602Ser

c.1804C>A · rs754298498 · VCV906102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa

Computational evidence

Protein change
AlphaMissense	0.9993	likely pathogenic · top 1% in PDE6B
REVEL	0.758	pathogenic-leaning
SaProt	LLR -13.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -4.5, phastCons 0.14
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,490 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,236 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.Arg602Ser
Coding: c.1804C>A
MANE Select: NM_000283
dbSNP: rs754298498
Type: single nucleotide variant
Location: chr4:662590 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 602: the pdease domain

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

Disease context

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

Also linked: congenital stationary night blindness autosomal dominant 2

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.Arg602His Conflicting classifications of pathogenicity ★ ⚠ same residue
PDE6B p.Arg602= Benign/Likely benign ★★ same residue
PDE6B p.Arg602Cys Uncertain significance ★ ⚠ same residue
PDE6B p.Arg602Gly Uncertain significance ★ ⚠ same residue
PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.1107+3A>G Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.1832+1G>T Pathogenic ★★ same condition
PDE6B c.1921-9C>G 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-arg602ser (accessed [today's date]).

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