Is PRPH2 p.Cys165Phe (c.494G>T) pathogenic?

PRPH2 p.Cys165Phe (c.494G>T) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-10-17). Absent from gnomAD v4.1; Associated with retinitis pigmentosa.

What condition is associated with PRPH2 p.Cys165Phe (c.494G>T)?

PRPH2 p.Cys165Phe (c.494G>T) is associated with retinitis pigmentosa (ClinVar).

How common is PRPH2 p.Cys165Phe (c.494G>T) in the general population?

PRPH2 p.Cys165Phe (c.494G>T) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

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

PRPH2 p.Cys165Phe

c.494G>T · rs61755788 · VCV973717

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

retinitis pigmentosa

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.932	strongly pathogenic-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRPH2
Protein: p.Cys165Phe
Coding: c.494G>T
MANE Select: NM_000322
dbSNP: rs61755788
Type: single nucleotide variant
Location: chr6:42721841 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 165: 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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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.Cys165Arg Pathogenic ★★ same residue
PRPH2 p.Cys165Trp Likely pathogenic ★ same residue
PRPH2 p.Cys165Tyr Pathogenic ★ same residue
PRPH2 c.828+3A>T 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
PRPH2 p.Arg220Gln 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-cys165phe (accessed [today's date]).

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