Is PDE6B p.Thr305= (c.915G>A) pathogenic?

PDE6B p.Thr305= (c.915G>A) is classified Benign/Likely benign in PDE6B (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with retinitis pigmentosa.

What condition is associated with PDE6B p.Thr305= (c.915G>A)?

PDE6B p.Thr305= (c.915G>A) is associated with retinitis pigmentosa, congenital stationary night blindness autosomal dominant 2 (ClinVar).

How is Retinitis pigmentosa inherited?

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

PDE6B p.Thr305=

Q: How common is PDE6B p.Thr305= (c.915G>A) in the general population?

PDE6B p.Thr305= (c.915G>A) is common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.915G>A · rs75695239 · VCV138640

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 7.2%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -12	GERP -4.5
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.2% African / African-American · 5,402/75,030 alleles

Filtering AF 7.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.97%

Overall 4.27% 68,940/1,613,338 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.2%	14
Ashkenazi Jewishnot grpmax-eligible	6.44%	16
Finnishnot grpmax-eligible	5.45%	18
European (non-Finnish)	4.39%	23
Remaining individualsnot grpmax-eligible	3.99%	25
Middle Eastern	3.83%	26
Admixed American	3.16%	32
South Asian	1.97%	51
Amishnot grpmax-eligible	0.877%	114
East Asian	0.0356%	2,806

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.Thr305=
Coding: c.915G>A
dbSNP: rs75695239
Type: single nucleotide variant
Location: chr4:654142 (GRCh38)

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)

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-thr305 (accessed [today's date]).

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