Is PDE6B p.Asp205= (c.615C>T) pathogenic?

PDE6B p.Asp205= (c.615C>T) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-06-01). Rare (popmax 0.756%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PDE6B p.Asp205= (c.615C>T)?

PDE6B p.Asp205= (c.615C>T) is associated with retinitis pigmentosa, congenital stationary night blindness autosomal dominant 2 (ClinVar).

How common is PDE6B p.Asp205= (c.615C>T) in the general population?

PDE6B p.Asp205= (c.615C>T) is rare (popmax 0.756%, 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.Asp205=

c.615C>T · rs149293844 · VCV92768

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.756%, 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 -16	GERP -4.2
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.756% European (non-Finnish) · 8,914/1,179,662 alleles

Filtering AF 0.742% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.737%

Overall 0.671% 10,829/1,613,658 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.17%	46
European (non-Finnish)grpmax	0.756%	132
Remaining individualsnot grpmax-eligible	0.504%	198
Ashkenazi Jewishnot grpmax-eligible	0.206%	485
African / African-American	0.123%	815
Admixed American	0.085%	1,177
Middle Eastern	0.0165%	6,052
South Asian	0.00549%	18,215

Finnish 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.Asp205=
Coding: c.615C>T
MANE Select: NM_000283
dbSNP: rs149293844
Type: single nucleotide variant
Location: chr4:634823 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 205: 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 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
PDE6B p.Asp600Asn 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-asp205 (accessed [today's date]).

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