Is PRPF3 p.Pro433= (c.1299A>G) pathogenic?

PRPF3 p.Pro433= (c.1299A>G) is classified Likely benign in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). Absent from gnomAD v4.1.

How common is PRPF3 p.Pro433= (c.1299A>G) in the general population?

PRPF3 p.Pro433= (c.1299A>G) is absent from gnomAD v4.1 (gnomAD).

PRPF3 p.Pro433=

c.1299A>G · VCV3611395

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP 1.8, phastCons 0.95
Overall
CADD	8.21	PHRED · no single calibrated threshold — expert panels disagree

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.Pro433=
Coding: c.1299A>G
MANE Select: NM_004698
Type: single nucleotide variant
Location: chr1:150343325 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 433: the 'mediates interaction with sart3' region

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

Similar variants

PRPF3 p.Pro433Leu Uncertain significance ★ ⚠ same residue
PRPF3 p.Arg449Gly Pathogenic/Likely pathogenic ★★ same type
PRPF3 p.His499Pro Pathogenic ★★ same type
PRPF3 p.Pro493Ser Pathogenic ★★ same type
PRPF3 p.Thr494Met Pathogenic ★★ same type
PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same type
PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same type
PRPF3 p.Asp43Gly Uncertain significance ★★ ⚠ same type

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-pro433 (accessed [today's date]).

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