Is PDE6C p.Lys789= (c.2367G>A) pathogenic?

PDE6C p.Lys789= (c.2367G>A) is classified Uncertain significance in PDE6C (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-28). Very rare (popmax 0.000242%, nfe); Associated with achromatopsia.

What condition is associated with PDE6C p.Lys789= (c.2367G>A)?

PDE6C p.Lys789= (c.2367G>A) is associated with achromatopsia, cone dystrophy 4 (ClinVar).

How common is PDE6C p.Lys789= (c.2367G>A) in the general population?

PDE6C p.Lys789= (c.2367G>A) is very rare (popmax 0.000242%, nfe) (gnomAD).

How is Achromatopsia inherited?

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

PDE6C p.Lys789=

c.2367G>A · rs2058671471 · VCV877548

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000242%, nfe)

Conditions

achromatopsia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Overall
CADD	17.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000242% European (non-Finnish) · 2/825,466 alleles

Filtering AF 4e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.5e-05%

Overall 0.000163% 2/1,224,644 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: PDE6C
Protein: p.Lys789=
Coding: c.2367G>A
MANE Select: NM_006204
dbSNP: rs2058671471
Type: single nucleotide variant
Location: chr10:93662643 (GRCh38)
Gene constraint: LOEUF 0.976 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.53 · 7 PDB
Residue 789: an α-helix; a UniProt-annotated variant site (in achm5); the pdease domain

Full PDE6C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

achromatopsia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone dystrophy 4

For Achromatopsia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

PDE6C p.Lys789Asn Uncertain significance ★ ⚠ same residue
PDE6C p.Lys789Thr Uncertain significance ★ same residue
PDE6C c.1004+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.1269+1G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.2283+1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6C c.939+5G>A Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg238Ter Pathogenic/Likely pathogenic ★★ same condition
PDE6C p.Arg259Ter 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/pde6c-p-lys789 (accessed [today's date]).

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