Is PRPH2 p.Pro210Arg (c.629C>G) pathogenic?

PRPH2 p.Pro210Arg (c.629C>G) is classified Pathogenic/Likely pathogenic in PRPH2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-21). Very rare (popmax 0.000169%, nfe); Associated with patterned dystrophy of the retinal pigment epithelium.

What condition is associated with PRPH2 p.Pro210Arg (c.629C>G)?

PRPH2 p.Pro210Arg (c.629C>G) is associated with patterned dystrophy of the retinal pigment epithelium, vitelliform macular dystrophy 2, Stargardt disease (ClinVar).

How common is PRPH2 p.Pro210Arg (c.629C>G) in the general population?

PRPH2 p.Pro210Arg (c.629C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

PRPH2 p.Pro210Arg

c.629C>G · rs61755798 · VCV13173

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

patterned dystrophy of the retinal pigment epithelium

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.89	moderately pathogenic-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,034 alleles

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

Overall 0.000124% 2/1,614,186 alleles · very rare exomes 2/1,461,892 · genomes 0/152,294 · 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.Pro210Arg
Coding: c.629C>G
MANE Select: NM_000322
dbSNP: rs61755798
Type: single nucleotide variant
Location: chr6:42704564 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 210: a UniProt-annotated variant site (in rp7; decreased protein expression); a UniProt-annotated variant site (in mdpt1 and rp7; also in adult-onset foveomacular dystrophy with choroidal neovascularization); a UniProt-annotated variant site (in rp7)

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

Disease context

patterned dystrophy of the retinal pigment epithelium — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: vitelliform macular dystrophy 2 Stargardt disease vitelliform macular dystrophy 3

Similar variants

PRPH2 p.Pro210Ser Pathogenic/Likely pathogenic ★★ same residue
PRPH2 p.Pro210Ala Pathogenic ★★ same residue
PRPH2 p.Pro210Leu Pathogenic/Likely pathogenic ★★ same residue
PRPH2 p.Pro210= Likely benign ★★ same residue
PRPH2 p.Pro210His Likely pathogenic ★ same residue
PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.582-1G>C Pathogenic ★★ same condition
PRPH2 c.828+2T>C 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-pro210arg (accessed [today's date]).

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