Is PDE6B p.Lys692Arg (c.2075A>G) pathogenic?

PDE6B p.Lys692Arg (c.2075A>G) is classified Conflicting classifications of pathogenicity in PDE6B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-05). AlphaMissense: likely benign (0.0613); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with PDE6B p.Lys692Arg (c.2075A>G)?

PDE6B p.Lys692Arg (c.2075A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PDE6B p.Lys692Arg (c.2075A>G) in the general population?

PDE6B p.Lys692Arg (c.2075A>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about PDE6B p.Lys692Arg (c.2075A>G)?

AlphaMissense predicts likely benign (score 0.0613) — an in-silico prediction, not a clinical call.

PDE6B p.Lys692Arg

c.2075A>G · rs1305642045 · VCV1411998

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0613	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -5.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -4.5, phastCons 0.93
Regional constraint	o/e 1.03	unconstrained · MANE · 44 kb · p 0.27 · regional, not allelic
Overall
CADD	17.47	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 0.00133% African / African-American · 1/74,916 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,612,714 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,916
European (non-Finnish)	0.000848%	117,906

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.Lys692Arg
Coding: c.2075A>G
MANE Select: NM_000283
dbSNP: rs1305642045
Type: single nucleotide variant
Location: chr4:664167 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.72
Residue 692: the pdease domain

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

Similar variants

PDE6B p.Ala19Ser Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala341Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala34Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala589Thr Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala809Val Uncertain significance ★★ ⚠ same condition
PDE6B p.Ala845Glu Uncertain significance ★★ ⚠ same condition
PDE6B p.Arg304Cys Uncertain significance ★★ ⚠ same condition
PDE6B p.Arg531Pro Uncertain significance ★★ ⚠ 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-lys692arg (accessed [today's date]).

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