Is PRPH2 p.Pro219del (c.656_658del) pathogenic?

PRPH2 p.Pro219del (c.656658del) is classified Likely pathogenic in PRPH2 (ClinVar, Single submitter, 4 submitters; last evaluated 2024-01-30). No gnomAD frequency available for this variant; Associated with retinitis pigmentosa 7.

What condition is associated with PRPH2 p.Pro219del (c.656_658del)?

PRPH2 p.Pro219del (c.656_658del) is associated with retinitis pigmentosa 7 (ClinVar).

How common is PRPH2 p.Pro219del (c.656_658del) in the general population?

PRPH2 p.Pro219del (c.656_658del) is no gnomAD frequency available for this variant (gnomAD).

How is Leber congenital amaurosis inherited?

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

PRPH2 p.Pro219del

c.656_658del · rs61755807 · VCV98697

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

retinitis pigmentosa 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PRPH2
Protein: p.Pro219del
Coding: c.656_658del
MANE Select: NM_000322
dbSNP: rs61755807
Type: Deletion
Location: chr6:42704535 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 219: a UniProt-annotated variant site (in some patients with macular dystrophy); a UniProt-annotated variant site (in rp7)

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

Disease context

retinitis pigmentosa 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PRPH2 p.Pro219fs Pathogenic ★ same residue
PRPH2 p.Gly305fs Pathogenic ★★ same condition
PRPH2 p.Leu307fs Pathogenic ★★ same condition
PRPH2 p.Pro219Thr Uncertain significance ★★ same residue
PRPH2 p.Pro219Ala Likely pathogenic ★ same residue
PRPH2 p.Pro219Arg Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Pro219Ser Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Pro219= Likely benign ★ same residue

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-pro219del (accessed [today's date]).

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