PRPH2

Chr 6ADARDigenic dominant

peripherin 2

NCBI Gene: 5961 ENSG00000112619 UniProt: P23942

Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure (By similarity). Required for the maintenance of retinal outer nuclear layer thickness (By similarity). Required for the correct development and organization of the photoreceptor inner segment (By similarity)

Primary Disease Associations & Inheritance

Choroidal dystrophy, central areolar 2MIM #613105

Leber congenital amaurosis 18MIM #608133

ADARDigenic dominant

Macular dystrophy, patterned, 1MIM #169150

Macular dystrophy, vitelliform, 3MIM #608161

Retinitis pigmentosa 7 and digenic formMIM #608133

ADARDigenic dominant

Retinitis punctata albescensMIM #136880

ADAR

299

ClinVar variants

111

Pathogenic / LP

0.12

pLI score

Active trials

Clinical Summary— PRPH2

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Gene-Disease Validity (ClinGen)

PRPH2-related retinopathy · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

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ClinVar Variants

111 Pathogenic / Likely Pathogenic· 122 VUS of 299 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.67LOEUF

pLI 0.116

Z-score 2.44

OE 0.29 (0.14–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.10Z-score

OE missense 0.98 (0.87–1.10)

189 obs / 193.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.29 (0.14–0.67)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.87–1.10)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05

0≤1.21.6

LoF obs/exp: 4 / 13.8Missense obs/exp: 189 / 193.0Syn Z: -0.39

ClinVar Variant Classifications

299 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic72

Likely Pathogenic39

VUS122

Likely Benign63

Conflicting3

Pathogenic

Likely Pathogenic

122

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	34	5	33	0	72
Likely Pathogenic	4	32	3	0	39
VUS	1	105	13	3	122
Likely Benign	0	1	14	48	63
Benign	0	0	0	0	0
Conflicting	—				3
Total	39	143	63	51	299

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PRPH2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PRPH2-related macular dystrophy

definitive

ADUndeterminedUncertain

Eye

G2P ↗

PRPH2-related retinitis pigmentosa

definitive

ARUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

PRPH2-related Leber congenital amaurosis

definitive

ARLoss Of FunctionAbsent Gene Product

Eye

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

PERIPHERIN 2; PRPH2

MIM #179605 · *

Choroidal dystrophy, central areolar 2

MIM #613105