Is PRPH2 p.Leu45Phe (c.133C>T) pathogenic?

PRPH2 p.Leu45Phe (c.133C>T) is classified Benign/Likely benign in PRPH2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-09). Low-frequency (popmax 1.42%, afr); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Leu45Phe (c.133C>T)?

PRPH2 p.Leu45Phe (c.133C>T) is associated with PRPH2-related disorder, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Leu45Phe (c.133C>T) in the general population?

PRPH2 p.Leu45Phe (c.133C>T) is low-frequency (popmax 1.42%, afr) (gnomAD).

PRPH2 p.Leu45Phe

c.133C>T · rs61755770 · VCV98653

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, afr)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.52	indeterminate
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% African / African-American · 1,069/75,036 alleles

Filtering AF 1.35% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 0.0795% 1,284/1,614,176 alleles · low-frequency exomes 693/1,461,888 · genomes 591/152,288 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.42%	70
Middle Eastern	0.132%	758
Remaining individualsnot grpmax-eligible	0.118%	845
Admixed American	0.0933%	1,072
South Asian	0.00878%	11,386
European (non-Finnish)	0.00585%	17,102

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.Leu45Phe
Coding: c.133C>T
MANE Select: NM_000322
dbSNP: rs61755770
Type: single nucleotide variant
Location: chr6:42722202 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 45: a UniProt-annotated variant site (in rp7 and vmd3; results in retinitis pigmentosa in combination with a null mutation of rom1)

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

Disease context

Also linked: fundus albipunctatus patterned macular dystrophy 1 adult-onset foveomacular vitelliform dystrophy choroidal dystrophy, central areolar 2 cone-rod dystrophy retinitis pigmentosa

Similar variants

PRPH2 c.582-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPH2 c.828+1G>A Pathogenic ★★ same condition
PRPH2 c.828+1G>T Pathogenic ★★ same condition
PRPH2 c.828+2T>C Pathogenic/Likely pathogenic ★★ same condition
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

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-leu45phe (accessed [today's date]).

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