Is PRPH2 p.Asp87fs (c.259_266del) pathogenic?

PRPH2 p.Asp87fs (c.259266del) is classified Pathogenic in PRPH2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-01-08). Very rare (popmax 0.000678%, nfe); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Asp87fs (c.259_266del)?

PRPH2 p.Asp87fs (c.259_266del) is associated with PRPH2-related disorder, inherited retinal dystrophy, Stargardt disease (ClinVar).

How common is PRPH2 p.Asp87fs (c.259_266del) in the general population?

PRPH2 p.Asp87fs (c.259_266del) is very rare (popmax 0.000678%, nfe) (gnomAD).

PRPH2 p.Asp87fs

c.259_266del · rs1554270834 · VCV437964

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,036 alleles

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

Overall 0.000496% 8/1,614,172 alleles · very rare exomes 8/1,461,892 · genomes 0/152,280 · 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.Asp87fs
Coding: c.259_266del
MANE Select: NM_000322
dbSNP: rs1554270834
Type: Deletion
Location: chr6:42722069 (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

Also linked: inherited retinal dystrophy Stargardt disease

Similar variants

PRPH2 p.Asn136fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Asp50fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Gln132fs Pathogenic ★★ same condition
PRPH2 p.Gly124fs Pathogenic ★★ same condition
PRPH2 p.Gly38fs Pathogenic ★★ same condition
PRPH2 p.Ile104fs Pathogenic ★★ same condition
PRPH2 p.Leu107fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Leu290fs 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-asp87fs (accessed [today's date]).

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