Is PDE6A p.Tyr28= (c.84C>T) pathogenic?

PDE6A p.Tyr28= (c.84C>T) is classified Benign/Likely benign in PDE6A (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Low-frequency (popmax 4.64%, afr); Associated with retinitis pigmentosa.

What condition is associated with PDE6A p.Tyr28= (c.84C>T)?

PDE6A p.Tyr28= (c.84C>T) is associated with retinitis pigmentosa, retinitis pigmentosa 43 (ClinVar).

How common is PDE6A p.Tyr28= (c.84C>T) in the general population?

PDE6A p.Tyr28= (c.84C>T) is low-frequency (popmax 4.64%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6A p.Tyr28=

c.84C>T · rs34230349 · VCV352008

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.64%, afr)

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 2.1	GERP -2.5, phastCons 1
Overall
CADD	1.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.64% African / African-American · 3,476/74,982 alleles

Filtering AF 4.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.45%

Overall 0.294% 4,742/1,614,034 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.64%	22
South Asian	0.573%	174
Remaining individualsnot grpmax-eligible	0.522%	192
Admixed American	0.308%	324
East Asian	0.283%	353
Middle Eastern	0.181%	551
European (non-Finnish)	0.00805%	12,421

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.Tyr28=
Coding: c.84C>T
MANE Select: NM_000440
dbSNP: rs34230349
Type: single nucleotide variant
Location: chr5:149944590 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80

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: retinitis pigmentosa 43

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.Tyr28Ter 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.1620+2T>A Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.1926+1G>A Pathogenic ★★ same condition
PDE6A c.1927-1G>C Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.2027+2T>G 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/pde6a-p-tyr28 (accessed [today's date]).

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