Is PRPH2 p.Pro296= (c.888C>T) pathogenic?

PRPH2 p.Pro296= (c.888C>T) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-17). Very rare (popmax 0.00661%, nfe); Associated with patterned macular dystrophy 1.

What condition is associated with PRPH2 p.Pro296= (c.888C>T)?

PRPH2 p.Pro296= (c.888C>T) is associated with patterned macular dystrophy 1, fundus albipunctatus, adult-onset foveomacular vitelliform dystrophy (ClinVar).

How common is PRPH2 p.Pro296= (c.888C>T) in the general population?

PRPH2 p.Pro296= (c.888C>T) is very rare (popmax 0.00661%, nfe) (gnomAD).

PRPH2 p.Pro296=

c.888C>T · rs183714869 · VCV498453

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Conditions

patterned macular dystrophy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -15	GERP -3
Overall
CADD	0.032	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% European (non-Finnish) · 78/1,179,998 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00502% 81/1,614,126 alleles · very rare exomes 73/1,461,834 · genomes 8/152,292 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,128
Remaining individualsnot grpmax-eligible	0.0032%	31,254
African / African-American	0.00133%	75,028

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRPH2
Protein: p.Pro296=
Coding: c.888C>T
MANE Select: NM_000322
dbSNP: rs183714869
Type: single nucleotide variant
Location: chr6:42698448 (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

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

Also linked: fundus albipunctatus adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy retinitis pigmentosa

Similar variants

PRPH2 c.828+3A>T Pathogenic ★★ same condition
PRPH2 c.829-4C>G 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.Arg195Gln Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Arg195Leu Pathogenic ★★ same condition
PRPH2 p.Arg195Ter 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-pro296 (accessed [today's date]).

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