Is PRPH2 p.Cys166= (c.498C>T) pathogenic?

PRPH2 p.Cys166= (c.498C>T) is classified Likely benign in PRPH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-23). Ultra-rare (popmax 0.0329%, mid); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Cys166= (c.498C>T)?

PRPH2 p.Cys166= (c.498C>T) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Cys166= (c.498C>T) in the general population?

PRPH2 p.Cys166= (c.498C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

PRPH2 p.Cys166=

c.498C>T · rs759752477 · VCV1122974

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.8	GERP -3.3
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00291% 47/1,614,088 alleles · ultra-rare exomes 42/1,461,890 · genomes 5/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0048%	20,830
European (non-Finnish)	0.00314%	31,893
African / African-American	0.00267%	37,464
South Asian	0.0022%	45,544
Admixed American	0.00167%	59,998

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.Cys166=
Coding: c.498C>T
MANE Select: NM_000322
dbSNP: rs759752477
Type: single nucleotide variant
Location: chr6:42721837 (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

PRPH2-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPH2 p.Cys166Ter Pathogenic ★★ same residue
PRPH2 p.Cys166Trp Uncertain significance ★ same residue
PRPH2 p.Cys166Tyr Conflicting classifications of pathogenicity ★ same residue
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

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-cys166 (accessed [today's date]).

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