Is PDE6A p.Thr679= (c.2037G>A) pathogenic?

PDE6A p.Thr679= (c.2037G>A) is classified Conflicting classifications of pathogenicity in PDE6A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-03). Ultra-rare (popmax 0.0283%, amr); Associated with retinitis pigmentosa.

What condition is associated with PDE6A p.Thr679= (c.2037G>A)?

PDE6A p.Thr679= (c.2037G>A) is associated with retinitis pigmentosa (ClinVar).

How common is PDE6A p.Thr679= (c.2037G>A) in the general population?

PDE6A p.Thr679= (c.2037G>A) is ultra-rare (popmax 0.0283%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PDE6A p.Thr679=

c.2037G>A · rs140267699 · VCV906869

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0283%, amr)

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 -20
Overall
CADD	0.036	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0283% Admixed American · 17/59,994 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00422% 68/1,609,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0283%	3,529
East Asian	0.0178%	5,606
South Asian	0.0165%	6,063
Remaining individualsnot grpmax-eligible	0.00641%	15,588
African / African-American	0.00267%	37,469
European (non-Finnish)	0.00187%	53,457

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.Thr679=
Coding: c.2037G>A
MANE Select: NM_000440
dbSNP: rs140267699
Type: single nucleotide variant
Location: chr5:149883527 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 679: the pdease 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

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.Thr679Arg Uncertain significance ★★ ⚠ same residue
PDE6A p.Thr679Met Uncertain significance ★★ ⚠ same residue
PDE6A c.1065+2T>A 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
PDE6A c.998+1G>A 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-thr679 (accessed [today's date]).

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