Is PRPH2 p.Arg310del (c.927GAG[1]) pathogenic?

PRPH2 p.Arg310del (c.927GAG[1]) is classified Uncertain significance in PRPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-24). Ultra-rare (popmax 0.011%, sas); Associated with PRPH2-related disorder.

What condition is associated with PRPH2 p.Arg310del (c.927GAG[1])?

PRPH2 p.Arg310del (c.927GAG[1]) is associated with PRPH2-related disorder (ClinVar).

How common is PRPH2 p.Arg310del (c.927GAG[1]) in the general population?

PRPH2 p.Arg310del (c.927GAG[1]) is ultra-rare (popmax 0.011%, sas) (gnomAD).

PRPH2 p.Arg310del

c.927GAG[1] · VCV3665257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

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 · substitutions only
Constraint at this position
Conservation	phyloP -3.9	GERP -3

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,076 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00062% 10/1,613,804 alleles · ultra-rare exomes 10/1,461,534 · genomes 0/152,270 · 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.Arg310del
Coding: c.927GAG[1]
MANE Select: NM_000322
Type: Microsatellite
Location: chr6:42698404 (GRCh38)
Gene constraint: LOEUF 0.773 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 1 PDB
Residue 310: a UniProt-annotated variant site (in)

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.Arg310fs Likely pathogenic ★ same residue
PRPH2 p.Arg310Lys Benign ★★ same residue
PRPH2 p.Arg310Glu Uncertain significance ★ same residue
PRPH2 p.Lys154del Pathogenic ★★ same condition
PRPH2 p.Ser322fs Pathogenic/Likely pathogenic ★★ same condition
PRPH2 p.Asn169del Likely pathogenic ★ same condition
PRPH2 p.Cys119del Pathogenic ★ same condition
PRPH2 p.Gly31fs 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-arg310del (accessed [today's date]).

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