Is PRPH2 p.Arg195Ter (c.583C>T) pathogenic?

PRPH2 p.Arg195Ter (c.583C>T) is classified Pathogenic/Likely pathogenic in PRPH2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-08-20). Very rare (popmax 0.000169%, nfe); Associated with patterned macular dystrophy 1.

What condition is associated with PRPH2 p.Arg195Ter (c.583C>T)?

PRPH2 p.Arg195Ter (c.583C>T) is associated with patterned macular dystrophy 1, patterned dystrophy of the retinal pigment epithelium, inherited retinal dystrophy (ClinVar).

How common is PRPH2 p.Arg195Ter (c.583C>T) in the general population?

PRPH2 p.Arg195Ter (c.583C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

PRPH2 p.Arg195Ter

c.583C>T · rs1322278463 · VCV973722

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

patterned macular dystrophy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.97 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Overall
CADD	50.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,132 alleles · very rare exomes 2/1,461,866 · genomes 0/152,266 · joint denominator

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.Arg195Ter
Coding: c.583C>T
MANE Select: NM_000322
dbSNP: rs1322278463
Type: single nucleotide variant
Location: chr6:42704610 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 195: a UniProt-annotated variant site (in cacd2; increased protein expression)

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: patterned dystrophy of the retinal pigment epithelium inherited retinal dystrophy

Similar variants

PRPH2 p.Arg195Gln Pathogenic/Likely pathogenic ★★ same residue
PRPH2 p.Arg195Leu Pathogenic ★★ same residue
PRPH2 p.Arg195Gly Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Arg195Pro Conflicting classifications of pathogenicity ★ same residue
PRPH2 c.581+1G>A Pathogenic ★★ same condition
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.582-2A>T Pathogenic ★★ same condition
PRPH2 c.828+3A>T 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-arg195ter (accessed [today's date]).

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