Is PDE6B p.Trp807Arg (c.2419T>C) pathogenic?

PDE6B p.Trp807Arg (c.2419T>C) is classified Pathogenic in PDE6B (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-22). AlphaMissense: likely pathogenic (0.9996); Very rare (popmax 0.00134%, afr); Associated with inherited retinal dystrophy.

What condition is associated with PDE6B p.Trp807Arg (c.2419T>C)?

PDE6B p.Trp807Arg (c.2419T>C) is associated with inherited retinal dystrophy (ClinVar).

How common is PDE6B p.Trp807Arg (c.2419T>C) in the general population?

PDE6B p.Trp807Arg (c.2419T>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PDE6B p.Trp807Arg (c.2419T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

PDE6B p.Trp807Arg

c.2419T>C · rs121918583 · VCV1068671

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 1% in PDE6B
REVEL	0.925	moderately pathogenic-leaning
SaProt	LLR -15.75	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,550 alleles

Overall 0.000661% 1/151,344 alleles · very rare

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.Trp807Arg
Coding: c.2419T>C
MANE Select: NM_000283
dbSNP: rs121918583
Type: single nucleotide variant
Location: chr4:667922 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 807: the pdease 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

Similar variants

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.1921-9C>G Pathogenic ★★ same condition
PDE6B p.Arg552Gln Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Arg552Trp Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Asp668Gly Pathogenic/Likely pathogenic ★★ same condition
PDE6B p.Asp776Asn 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-trp807arg (accessed [today's date]).

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