Is PDE6B p.Arg799Ter (c.2395C>T) pathogenic?

PDE6B p.Arg799Ter (c.2395C>T) is classified Pathogenic in PDE6B (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-04-09). Very rare (popmax 0.00133%, afr); Associated with PDE6B-related disorder.

What condition is associated with PDE6B p.Arg799Ter (c.2395C>T)?

PDE6B p.Arg799Ter (c.2395C>T) is associated with PDE6B-related disorder, oculocutaneous albinism type 2, retinitis pigmentosa 40 (ClinVar).

How common is PDE6B p.Arg799Ter (c.2395C>T) in the general population?

PDE6B p.Arg799Ter (c.2395C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

PDE6B p.Arg799Ter

c.2395C>T · rs970990957 · VCV620164

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

PDE6B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.32	GERP -4.5, phastCons 0.061
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,002 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00116% 17/1,461,210 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,002
European (non-Finnish)	0.00127%	78,645
South Asian	0.0011%	91,072

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.Arg799Ter
Coding: c.2395C>T
MANE Select: NM_007100 · reported on NM_000283
dbSNP: rs970990957
Type: single nucleotide variant
Location: chr4:667898 (GRCh38)

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

Disease context

PDE6B-related disorder

Also linked: oculocutaneous albinism type 2 retinitis pigmentosa 40 inherited retinal dystrophy retinitis pigmentosa

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-arg799ter (accessed [today's date]).

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