Is PRPH2 p.Ser76fs (c.227_230del) pathogenic?

PRPH2 p.Ser76fs (c.227230del) is classified Likely pathogenic in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-03). Very rare (popmax 8.47e-05%, nfe); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Ser76fs (c.227_230del)?

PRPH2 p.Ser76fs (c.227_230del) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Ser76fs (c.227_230del) in the general population?

PRPH2 p.Ser76fs (c.227_230del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

PRPH2 p.Ser76fs

c.227_230del · VCV4891996

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

PRPH2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.2e-05% 1/1,614,200 alleles · very rare exomes 1/1,461,892 · genomes 0/152,308 · joint denominator

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.Ser76fs
Coding: c.227_230del
MANE Select: NM_000322
Type: Deletion
Location: chr6:42722105 (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.Ser76Ter Pathogenic ★★ same residue
PRPH2 p.Ser76= Likely benign ★ same residue
PRPH2 p.Asn136fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Asp50fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Asp87fs Pathogenic ★★ same condition
PRPH2 p.Gln132fs Pathogenic ★★ same condition
PRPH2 p.Gly38fs Pathogenic ★★ same condition
PRPH2 p.Leu290fs 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-ser76fs (accessed [today's date]).

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