Is PDE6B p.Thr233= (c.699G>A) pathogenic?

PDE6B p.Thr233= (c.699G>A) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-28). Rare (popmax 0.272%, eas); Associated with inherited retinal dystrophy.

What condition is associated with PDE6B p.Thr233= (c.699G>A)?

PDE6B p.Thr233= (c.699G>A) is associated with inherited retinal dystrophy, congenital stationary night blindness autosomal dominant 2, retinitis pigmentosa (ClinVar).

How common is PDE6B p.Thr233= (c.699G>A) in the general population?

PDE6B p.Thr233= (c.699G>A) is rare (popmax 0.272%, eas) (gnomAD).

PDE6B p.Thr233=

c.699G>A · rs148264146 · VCV349314

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.272%, eas)

Conditions

inherited retinal dystrophy

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 -12	GERP -4.2
Overall
CADD	0.591	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.272% East Asian · 122/44,848 alleles

Filtering AF 0.233% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.218%

Overall 0.00985% 158/1,603,716 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.272%	368
Middle Eastern	0.0165%	6,046
African / African-American	0.0107%	9,357
South Asian	0.00881%	11,356
Remaining individualsnot grpmax-eligible	0.00322%	31,072
European (non-Finnish)	0.00145%	68,854

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.Thr233=
Coding: c.699G>A
MANE Select: NM_000283
dbSNP: rs148264146
Type: single nucleotide variant
Location: chr4:635957 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 233: the gaf 2 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: congenital stationary night blindness autosomal dominant 2 retinitis pigmentosa

Similar variants

PDE6B p.Thr233Met Uncertain significance ★★ ⚠ same residue
PDE6B p.Thr233Lys 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.1468-2A>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

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-thr233 (accessed [today's date]).

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