Is PDE6A p.Glu59= (c.177A>G) pathogenic?

PDE6A p.Glu59= (c.177A>G) is classified Benign in PDE6A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-24). Low-frequency (popmax 1.48%, sas); Associated with retinitis pigmentosa.

What condition is associated with PDE6A p.Glu59= (c.177A>G)?

PDE6A p.Glu59= (c.177A>G) is associated with retinitis pigmentosa, inherited retinal dystrophy (ClinVar).

How common is PDE6A p.Glu59= (c.177A>G) in the general population?

PDE6A p.Glu59= (c.177A>G) is low-frequency (popmax 1.48%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6A p.Glu59=

c.177A>G · rs146550067 · VCV782818

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.48%, sas)

Conditions

retinitis pigmentosa

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 -1.1	GERP -5.5
Overall
CADD	4.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.48% South Asian · 1,344/91,080 alleles

Filtering AF 1.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.38%

Overall 0.166% 2,687/1,614,108 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.48%	68
Middle Eastern	0.214%	466
Remaining individualsnot grpmax-eligible	0.189%	530
European (non-Finnish)	0.0984%	1,016
Admixed American	0.03%	3,334
East Asian	0.0267%	3,740
African / African-American	0.0213%	4,689
Finnishnot grpmax-eligible	0.00625%	16,003
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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: PDE6A
Protein: p.Glu59=
Coding: c.177A>G
MANE Select: NM_000440
dbSNP: rs146550067
Type: single nucleotide variant
Location: chr5:149944497 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 59: the gaf 1 domain

Full PDE6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Also linked: inherited retinal dystrophy

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PDE6A p.Glu59Lys Uncertain significance ★ ⚠ same residue
PDE6A p.Glu59Ter Likely pathogenic ★ same residue
PDE6A c.1065+2T>A Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.1407+1G>C Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.1620+1G>A Pathogenic ★★ same condition
PDE6A c.1926+1G>A Pathogenic ★★ same condition
PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.627+2T>G 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/pde6a-p-glu59 (accessed [today's date]).

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