Is PRPH2 p.Val268Phe (c.802G>T) pathogenic?

PRPH2 p.Val268Phe (c.802G>T) is classified Uncertain significance in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). Very rare (popmax 0.00134%, afr); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Val268Phe (c.802G>T)?

PRPH2 p.Val268Phe (c.802G>T) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Val268Phe (c.802G>T) in the general population?

PRPH2 p.Val268Phe (c.802G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

PRPH2 p.Val268Phe

c.802G>T · rs62645936 · VCV1443011

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.126	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.88	GERP -1.9
Regional constraint	o/e 0.98	unconstrained · MANE · 24 kb · p 0.64 · regional, not allelic
Overall
CADD	6.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,846 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000497% 8/1,609,430 alleles · very rare exomes 7/1,457,328 · genomes 1/152,102 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,338
African / African-Americangrpmax	0.00134%	74,846
South Asian	0.00111%	90,254
European (non-Finnish)	0.000424%	235,612

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val268Phe
Coding: c.802G>T
MANE Select: NM_000322
dbSNP: rs62645936
Type: single nucleotide variant
Location: chr6:42704391 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 268: a UniProt-annotated variant site (in vmd3)

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.Val268Ala Uncertain significance ★ same residue
PRPH2 p.Val268Ile Conflicting classifications of pathogenicity ★ same residue
PRPH2 p.Val268Leu Uncertain significance ★ 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-val268phe (accessed [today's date]).

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