Is PDE6B p.His620Arg (c.1859A>G) pathogenic?

PDE6B p.His620Arg (c.1859A>G) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-08). AlphaMissense: likely pathogenic (0.9576); Very rare (popmax 0.00134%, afr); Associated with retinitis pigmentosa 40.

What condition is associated with PDE6B p.His620Arg (c.1859A>G)?

PDE6B p.His620Arg (c.1859A>G) is associated with retinitis pigmentosa 40, inherited retinal dystrophy (ClinVar).

How common is PDE6B p.His620Arg (c.1859A>G) in the general population?

PDE6B p.His620Arg (c.1859A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about PDE6B p.His620Arg (c.1859A>G)?

AlphaMissense predicts likely pathogenic (score 0.9576) — an in-silico prediction, not a clinical call.

PDE6B p.His620Arg

c.1859A>G · rs1737315492 · VCV931852

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9576 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 40

Computational evidence

Protein change
AlphaMissense	0.9576	likely pathogenic
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -8.53	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 2.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	24.4	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 · 1/74,854 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,611,616 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,854
European (non-Finnish)	0.00034%	294,493

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.His620Arg
Coding: c.1859A>G
MANE Select: NM_000283
dbSNP: rs1737315492
Type: single nucleotide variant
Location: chr4:663126 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 620: the pdease domain

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

Disease context

retinitis pigmentosa 40 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PDE6B p.His620fs Pathogenic ★★ same residue
PDE6B p.His620Gln Uncertain significance ★ ⚠ same residue
PDE6B p.His620Tyr Uncertain significance ★ same residue
PDE6B p.His620= Likely benign ★ same residue
PDE6B c.1059+2T>G Likely pathogenic ★★ same condition
PDE6B c.1060-1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.1107+1G>T Likely pathogenic ★★ same condition
PDE6B c.1107+3A>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-his620arg (accessed [today's date]).

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