Is PRPH2 p.Arg284= (c.852C>A) pathogenic?

PRPH2 p.Arg284= (c.852C>A) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-04). Very rare (popmax 0.000678%, nfe); Associated with retinitis pigmentosa.

What condition is associated with PRPH2 p.Arg284= (c.852C>A)?

PRPH2 p.Arg284= (c.852C>A) is associated with retinitis pigmentosa, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Arg284= (c.852C>A) in the general population?

PRPH2 p.Arg284= (c.852C>A) is very rare (popmax 0.000678%, nfe) (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPH2 p.Arg284=

c.852C>A · rs745807357 · VCV909882

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -0.63, phastCons 1
Overall
CADD	4.498	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,046 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,614,210 alleles · very rare exomes 8/1,461,878 · genomes 0/152,332 · joint denominator

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: PRPH2
Protein: p.Arg284=
Coding: c.852C>A
MANE Select: NM_000322
dbSNP: rs745807357
Type: single nucleotide variant
Location: chr6:42698484 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB

Full PRPH2 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: fundus albipunctatus patterned macular dystrophy 1 adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy

For Retinitis pigmentosa (Orphanet):

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

Similar variants

PRPH2 p.Arg284Cys Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Arg284Pro Uncertain significance ★ same residue
PRPH2 p.Arg284His Likely pathogenic same residue
PRPH2 c.828+3A>T Pathogenic ★★ same condition
PRPH2 c.829-4C>G Pathogenic ★★ same condition
PRPH2 p.Arg142Trp Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg172Gln Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg172Trp 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/prph2-p-arg284 (accessed [today's date]).

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