Is PRPF3 p.Pro166Arg (c.497C>G) pathogenic?

PRPF3 p.Pro166Arg (c.497C>G) is classified Uncertain significance in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-01). AlphaMissense: likely benign (0.1835); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with PRPF3 p.Pro166Arg (c.497C>G)?

PRPF3 p.Pro166Arg (c.497C>G) is associated with inherited retinal dystrophy (ClinVar).

How common is PRPF3 p.Pro166Arg (c.497C>G) in the general population?

PRPF3 p.Pro166Arg (c.497C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPF3 p.Pro166Arg (c.497C>G)?

AlphaMissense predicts likely benign (score 0.1835) — an in-silico prediction, not a clinical call.

PRPF3 p.Pro166Arg

c.497C>G · rs2525116191 · VCV3028175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1835	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -8.16	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 331 bp · p 0.14 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRPF3
Protein: p.Pro166Arg
Coding: c.497C>G
MANE Select: NM_004698
dbSNP: rs2525116191
Type: single nucleotide variant
Location: chr1:150332757 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 166: the 'disordered' region

Full PRPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPF3 p.Pro166= Likely benign ★★ same residue
PRPF3 p.Pro493Ser Pathogenic ★★ same condition
PRPF3 p.Thr494Met Pathogenic ★★ same condition
PRPF3 p.Gln461Glu Uncertain significance ★★ ⚠ same condition
PRPF3 p.Ile560Met Uncertain significance ★★ ⚠ same condition
PRPF3 p.Lys662Arg Uncertain significance ★★ ⚠ same condition
PRPF3 p.Ala673= Benign/Likely benign ★★ same condition
PRPF3 p.Leu235= Likely benign ★★ 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/prpf3-p-pro166arg (accessed [today's date]).

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