Is PRPH2 p.Tyr236= (c.708C>T) pathogenic?

PRPH2 p.Tyr236= (c.708C>T) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-05). Rare (popmax 0.192%, afr); Associated with retinitis pigmentosa.

What condition is associated with PRPH2 p.Tyr236= (c.708C>T)?

PRPH2 p.Tyr236= (c.708C>T) is associated with retinitis pigmentosa, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Tyr236= (c.708C>T) in the general population?

PRPH2 p.Tyr236= (c.708C>T) is rare (popmax 0.192%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PRPH2 p.Tyr236=

c.708C>T · rs61755813 · VCV98702

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.192%, afr)

Conditions

retinitis pigmentosa

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 -8.4	GERP -2.8
Overall
CADD	0.662	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.192% African / African-American · 144/75,056 alleles

Filtering AF 0.166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.157%

Overall 0.0114% 184/1,614,104 alleles · rare exomes 88/1,461,790 · genomes 96/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.192%	521
Admixed American	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Middle Eastern	0.0165%	6,062
South Asian	0.00659%	15,177
European (non-Finnish)	0.000339%	294,999

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.Tyr236=
Coding: c.708C>T
MANE Select: NM_000322
dbSNP: rs61755813
Type: single nucleotide variant
Location: chr6:42704485 (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

retinitis pigmentosa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRPH2 p.Tyr236Ter Pathogenic ★★ same residue
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

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-tyr236 (accessed [today's date]).

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