Is PDE6C p.Leu179= (c.537G>T) pathogenic?

PDE6C p.Leu179= (c.537G>T) is classified Conflicting classifications of pathogenicity in PDE6C (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-03). Very rare (popmax 0.00271%, nfe); Associated with achromatopsia.

What condition is associated with PDE6C p.Leu179= (c.537G>T)?

PDE6C p.Leu179= (c.537G>T) is associated with achromatopsia, cone dystrophy 4 (ClinVar).

How common is PDE6C p.Leu179= (c.537G>T) in the general population?

PDE6C p.Leu179= (c.537G>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

How is Achromatopsia inherited?

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

PDE6C p.Leu179=

c.537G>T · rs752478645 · VCV877399

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00271%, 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 4	GERP -0.82, phastCons 1
Overall
CADD	7.794	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,180,000 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00235% 38/1,614,020 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)grpmax	0.00271%	36,875
African / African-American	0.00133%	74,920

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu179=
Coding: c.537G>T
MANE Select: NM_006204
dbSNP: rs752478645
Type: single nucleotide variant
Location: chr10:93620688 (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 179: the gaf 1 domain; a β-strand

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 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
PDE6C p.Arg29Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PDE6C p.Arg527Ter 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-leu179 (accessed [today's date]).

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