Is PDE6G p.Pro27= (c.81C>T) pathogenic?

PDE6G p.Pro27= (c.81C>T) is classified Conflicting classifications of pathogenicity in PDE6G (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-06-11). Rare (popmax 0.231%, sas); Associated with retinitis pigmentosa.

What condition is associated with PDE6G p.Pro27= (c.81C>T)?

PDE6G p.Pro27= (c.81C>T) is associated with retinitis pigmentosa (ClinVar).

How common is PDE6G p.Pro27= (c.81C>T) in the general population?

PDE6G p.Pro27= (c.81C>T) is rare (popmax 0.231%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6G p.Pro27=

c.81C>T · rs546019967 · VCV889345

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.231%, 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 0.057	GERP -5.3, phastCons 0.84
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.231% South Asian · 210/91,084 alleles

Filtering AF 0.205% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.195%

Overall 0.0141% 228/1,614,124 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.231%	434
Remaining individualsnot grpmax-eligible	0.0208%	4,808
African / African-American	0.00666%	15,009

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: PDE6G
Protein: p.Pro27=
Coding: c.81C>T
MANE Select: NM_002602
dbSNP: rs546019967
Type: single nucleotide variant
Location: chr17:81653225 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.73 · 1 PDB
Residue 27: the 'disordered' region; a UniProt-annotated variant site (sequence variant)

Full PDE6G 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

For Retinitis pigmentosa (Orphanet):

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

Similar variants

PDE6G p.Pro27Ser Uncertain significance ★ same residue
PDE6G p.Gly59Ser Uncertain significance ★★ ⚠ same condition
PDE6G p.Pro5Leu Uncertain significance ★★ ⚠ same condition
PDE6G c.*233T>C Benign ★★ same condition
PDE6G c.*274C>T Benign ★★ same condition
PDE6G c.*316G>A Benign ★★ same condition
PDE6G c.*393C>T Benign ★★ same condition
PDE6G c.*399C>T Benign ★★ 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/pde6g-p-pro27 (accessed [today's date]).

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