Is PRPH2 p.Tyr83= (c.249C>T) pathogenic?

PRPH2 p.Tyr83= (c.249C>T) is classified Conflicting classifications of pathogenicity in PRPH2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-01). Rare (popmax 0.132%, mid); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Tyr83= (c.249C>T)?

PRPH2 p.Tyr83= (c.249C>T) is associated with PRPH2-related disorder, fundus albipunctatus, patterned macular dystrophy 1 (ClinVar).

How common is PRPH2 p.Tyr83= (c.249C>T) in the general population?

PRPH2 p.Tyr83= (c.249C>T) is rare (popmax 0.132%, mid) (gnomAD).

PRPH2 p.Tyr83=

c.249C>T · rs61755775 · VCV98658

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.5	GERP -3.3
Overall
CADD	0.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,062 alleles

Filtering AF 0.0862% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0844%

Overall 0.0762% 1,230/1,614,160 alleles · rare exomes 1,149/1,461,890 · genomes 81/152,270 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
European (non-Finnish)	0.0908%	1,102
Ashkenazi Jewishnot grpmax-eligible	0.0878%	1,139
Remaining individualsnot grpmax-eligible	0.0624%	1,603
South Asian	0.0406%	2,462
Finnishnot grpmax-eligible	0.0359%	2,784
Admixed American	0.0217%	4,617
African / African-American	0.0133%	7,503
East Asian	0.00668%	14,959

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.Tyr83=
Coding: c.249C>T
MANE Select: NM_000322
dbSNP: rs61755775
Type: single nucleotide variant
Location: chr6:42722086 (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

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

Similar variants

PRPH2 p.Tyr83Ter Pathogenic ★ 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+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-tyr83 (accessed [today's date]).

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