Is PDE6B p.Arg705Gln (c.2114G>A) pathogenic?

PDE6B p.Arg705Gln (c.2114G>A) is classified Uncertain significance in PDE6B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-01). AlphaMissense: likely benign (0.2587); Ultra-rare (popmax 0.0312%, eas); Associated with inherited retinal dystrophy.

What condition is associated with PDE6B p.Arg705Gln (c.2114G>A)?

PDE6B p.Arg705Gln (c.2114G>A) is associated with inherited retinal dystrophy (ClinVar).

How common is PDE6B p.Arg705Gln (c.2114G>A) in the general population?

PDE6B p.Arg705Gln (c.2114G>A) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about PDE6B p.Arg705Gln (c.2114G>A)?

AlphaMissense predicts likely benign (score 0.2587) — an in-silico prediction, not a clinical call.

PDE6B p.Arg705Gln

c.2114G>A · rs200397909 · VCV1516914

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.2587	likely benign
REVEL	0.563	indeterminate
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP -0.03, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	28.7	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 0.0312% East Asian · 14/44,812 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00113% 18/1,599,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,201
African / African-American	0.00401%	24,923
European (non-Finnish)	8.57e-05%	1,166,769

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.Arg705Gln
Coding: c.2114G>A
MANE Select: NM_000283
dbSNP: rs200397909
Type: single nucleotide variant
Location: chr4:664206 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 705: 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 p.Arg705= Likely benign ★★ 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.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

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-arg705gln (accessed [today's date]).

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