Is PDE6B p.Arg472Cys (c.1414C>T) pathogenic?

PDE6B p.Arg472Cys (c.1414C>T) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1007); Rare (popmax 0.66%, sas); Associated with Inborn genetic diseases.

What condition is associated with PDE6B p.Arg472Cys (c.1414C>T)?

PDE6B p.Arg472Cys (c.1414C>T) is associated with Inborn genetic diseases, congenital stationary night blindness autosomal dominant 2, retinitis pigmentosa (ClinVar).

How common is PDE6B p.Arg472Cys (c.1414C>T) in the general population?

PDE6B p.Arg472Cys (c.1414C>T) is rare (popmax 0.66%, sas) (gnomAD).

What do computational predictors say about PDE6B p.Arg472Cys (c.1414C>T)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

PDE6B p.Arg472Cys

c.1414C>T · rs143908642 · VCV721487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.66%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.056	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	18.88	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 0.66% South Asian · 601/91,070 alleles

Filtering AF 0.616% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.599%

Overall 0.0436% 704/1,613,108 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.66%	152
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.048%	2,082
African / African-American	0.0467%	2,143
Admixed American	0.02%	5,001
Finnishnot grpmax-eligible	0.00314%	31,818
East Asian	0.00223%	44,878
European (non-Finnish)	0.0017%	58,972

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.Arg472Cys
Coding: c.1414C>T
MANE Select: NM_000283
dbSNP: rs143908642
Type: single nucleotide variant
Location: chr4:658964 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72

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

Disease context

Inborn genetic diseases — 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.Arg472His 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.1832+1G>T Pathogenic ★★ same condition
PDE6B c.1921-9C>G Pathogenic ★★ same condition
PDE6B c.2021+2T>G Pathogenic/Likely pathogenic ★★ same condition
PDE6B c.2193+1G>A Pathogenic ★★ same condition
PDE6B p.Arg560Cys 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-arg472cys (accessed [today's date]).

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