Is PRPH2 p.Arg142fs (c.423_424dup) pathogenic?

PRPH2 p.Arg142fs (c.423424dup) is classified Pathogenic in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Associated with patterned macular dystrophy 1.

What condition is associated with PRPH2 p.Arg142fs (c.423_424dup)?

PRPH2 p.Arg142fs (c.423_424dup) is associated with patterned macular dystrophy 1 (ClinVar).

PRPH2 p.Arg142fs

c.423_424dup · VCV4532240

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

patterned macular dystrophy 1

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 5.9	GERP 1.8, phastCons 1

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

Variant & gene context

Gene: PRPH2
Protein: p.Arg142fs
Coding: c.423_424dup
MANE Select: NM_000322
Type: Duplication
Location: chr6:42721910 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 142: a UniProt-annotated variant site (in rp7; also found in a patient with central areolar choroidal dystrophy)

Full PRPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

patterned macular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH2 p.Arg142Trp Pathogenic/Likely pathogenic ★★ same residue
PRPH2 p.Ser125fs Likely pathogenic ★ same condition
PRPH2 p.Ser289fs Pathogenic ★ same condition
PRPH2 p.Arg142Gln Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Tyr141fs Pathogenic same condition
PRPH2 c.828+3A>T Pathogenic ★★ same condition
PRPH2 c.829-4C>G 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-arg142fs (accessed [today's date]).

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