Is PRPF3 p.Pro493Ser (c.1477C>T) pathogenic?

PRPF3 p.Pro493Ser (c.1477C>T) is classified Pathogenic in PRPF3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-22). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with PRPF3 p.Pro493Ser (c.1477C>T)?

PRPF3 p.Pro493Ser (c.1477C>T) is associated with inherited retinal dystrophy, retinitis pigmentosa 18 (ClinVar).

How common is PRPF3 p.Pro493Ser (c.1477C>T) in the general population?

PRPF3 p.Pro493Ser (c.1477C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPF3 p.Pro493Ser (c.1477C>T)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

PRPF3 p.Pro493Ser

c.1477C>T · rs121434242 · VCV3353

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic ✓ concordant with ClinVar · top 3% in PRPF3
REVEL	0.987	strongly pathogenic-leaning
SaProt	LLR -13.47	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 7e-23 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

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.Pro493Ser
Coding: c.1477C>T
MANE Select: NM_004698
dbSNP: rs121434242
Type: single nucleotide variant
Location: chr1:150344212 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 493: a UniProt-annotated variant site (in rp18); an α-helix; the 'mediates interaction with sart3' 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

Also linked: retinitis pigmentosa 18

Similar variants

PRPF3 p.Pro493Ala Uncertain significance ★ ⚠ same residue
PRPF3 p.Pro493= Likely benign ★ same residue
PRPF3 p.Thr494Met Pathogenic ★★ same condition
PRPF3 p.Gln445Arg Uncertain significance ★★ same condition
PRPF3 p.Gln461Glu Uncertain significance ★★ ⚠ same condition
PRPF3 p.Ile560Met Uncertain significance ★★ ⚠ same condition
PRPF3 p.Lys662Arg Uncertain significance ★★ ⚠ same condition
PRPF3 c.1760-12C>T Benign/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-pro493ser (accessed [today's date]).

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