Is PRPF3 p.Ala489Asp (c.1466C>A) pathogenic?

PRPF3 p.Ala489Asp (c.1466C>A) is classified Pathogenic in PRPF3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-06-01). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 18.

What condition is associated with PRPF3 p.Ala489Asp (c.1466C>A)?

PRPF3 p.Ala489Asp (c.1466C>A) is associated with retinitis pigmentosa 18 (ClinVar).

How common is PRPF3 p.Ala489Asp (c.1466C>A) in the general population?

PRPF3 p.Ala489Asp (c.1466C>A) is absent from gnomAD v4.1 (gnomAD).

How is Retinitis pigmentosa inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRPF3 p.Ala489Asp (c.1466C>A)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

PRPF3 p.Ala489Asp

c.1466C>A · rs121434243 · VCV3354

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 18

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 3% in PRPF3
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -16.27	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	28.8	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.Ala489Asp
Coding: c.1466C>A
MANE Select: NM_004698
dbSNP: rs121434243
Type: single nucleotide variant
Location: chr1:150344201 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 489: 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

retinitis pigmentosa 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same residue
PRPF3 p.Ala489= Conflicting classifications of pathogenicity ★ same residue
PRPF3 p.Pro493Ser Pathogenic ★★ same condition
PRPF3 p.Thr494Met Pathogenic ★★ same condition
PRPF3 p.Gln445Arg Uncertain significance ★★ same condition
PRPF3 c.1760-12C>T Benign/Likely benign ★★ same condition
PRPF3 p.Ala502Pro Likely pathogenic ★ same condition
PRPF3 p.Asp429Tyr 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/prpf3-p-ala489asp (accessed [today's date]).

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