Is PDE6B p.Phe95= (c.285C>T) pathogenic?

PDE6B p.Phe95= (c.285C>T) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-06). Very rare (popmax 0.00298%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PDE6B p.Phe95= (c.285C>T)?

PDE6B p.Phe95= (c.285C>T) is associated with retinitis pigmentosa, congenital stationary night blindness autosomal dominant 2 (ClinVar).

How common is PDE6B p.Phe95= (c.285C>T) in the general population?

PDE6B p.Phe95= (c.285C>T) is very rare (popmax 0.00298%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6B p.Phe95=

c.285C>T · rs746211772 · VCV903743

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00298%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	GERP -0.24, phastCons 0.99
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00298% European (non-Finnish) · 35/1,175,066 alleles

Filtering AF 0.00216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00225% 36/1,602,164 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00298%	33,573
African / African-American	0.00134%	74,714

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.Phe95=
Coding: c.285C>T
MANE Select: NM_000283
dbSNP: rs746211772
Type: single nucleotide variant
Location: chr4:625911 (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 — 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.Phe95Ser 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
PDE6B c.2021+2T>G Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.2193+1G>A Pathogenic ★★ same condition
PDE6B p.Arg560Cys Pathogenic/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-phe95 (accessed [today's date]).

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