Is PRPH2 p.Phe74fs (c.219_220insAA) pathogenic?

PRPH2 p.Phe74fs (c.219220insAA) is classified Pathogenic in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Phe74fs (c.219_220insAA)?

PRPH2 p.Phe74fs (c.219_220insAA) is associated with PRPH2-related disorder (ClinVar).

PRPH2 p.Phe74fs

c.219_220insAA · VCV4719772

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 3.4	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: PRPH2
Protein: p.Phe74fs
Coding: c.219_220insAA
MANE Select: NM_000322
Type: Insertion
Location: chr6:42722115 (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

PRPH2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH2 p.Ser259_Ser260insLeu Uncertain significance ★★ same condition
PRPH2 p.Val14fs Pathogenic ★ same condition
PRPH2 p.Val200_Asp201insGlyProSerProValSerLeuSerLeuSerArgLeuProLeuProLeuProSerProSerProAlaProGluThrHisThrArgSerLeuIleGlnLeuProXaaXaaXaaXaaLysLysLysLysLysLysLysSerAsnVal Pathogenic ★ same condition
PRPH2 p.Gln304_Gly305insSerGlu Uncertain significance ★ same condition
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+1G>A Pathogenic ★★ same condition
PRPH2 c.828+1G>T Pathogenic ★★ same condition
PRPH2 c.828+2T>C 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-phe74fs (accessed [today's date]).

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