Is PDE6A p.Arg562Gln (c.1685G>A) pathogenic?

PDE6A p.Arg562Gln (c.1685G>A) is classified Likely pathogenic in PDE6A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-01-06). AlphaMissense: likely pathogenic (0.7729); Very rare (popmax 0.00768%, sas); Associated with retinitis pigmentosa 43.

What condition is associated with PDE6A p.Arg562Gln (c.1685G>A)?

PDE6A p.Arg562Gln (c.1685G>A) is associated with retinitis pigmentosa 43 (ClinVar).

How common is PDE6A p.Arg562Gln (c.1685G>A) in the general population?

PDE6A p.Arg562Gln (c.1685G>A) is very rare (popmax 0.00768%, sas) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about PDE6A p.Arg562Gln (c.1685G>A)?

AlphaMissense predicts likely pathogenic (score 0.7729) — an in-silico prediction, not a clinical call.

PDE6A p.Arg562Gln

c.1685G>A · rs373537826 · VCV961613

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7729 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00768%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 43

Computational evidence

Protein change
AlphaMissense	0.7729	likely pathogenic ✓ concordant with ClinVar
REVEL	0.785	moderately pathogenic-leaning
SaProt	LLR -11.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 77 kb · p 0.94 · regional, not allelic
Overall
CADD	28.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00768% South Asian · 7/91,088 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00223% 36/1,614,034 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00768%	13,013
African / African-American	0.00668%	14,981
Remaining individualsnot grpmax-eligible	0.0048%	20,828
East Asian	0.00223%	44,892
Admixed American	0.00167%	60,004
Finnishnot grpmax-eligible	0.00156%	64,034
European (non-Finnish)	0.00153%	65,557

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.Arg562Gln
Coding: c.1685G>A
MANE Select: NM_000440
dbSNP: rs373537826
Type: single nucleotide variant
Location: chr5:149895226 (GRCh38)
Gene constraint: LOEUF 0.888 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.80
Residue 562: the pdease domain

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

Disease context

retinitis pigmentosa 43 — 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.Arg562Trp Pathogenic/Likely pathogenic ★★ same residue
PDE6A c.1407+1G>C Pathogenic/Likely 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
PDE6A c.2135+1G>T Pathogenic/Likely pathogenic ★★ same condition
PDE6A c.2275-1G>A 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-arg562gln (accessed [today's date]).

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