Is PRPF3 p.Pro427Ser (c.1279C>T) pathogenic?

PRPF3 p.Pro427Ser (c.1279C>T) is classified Uncertain significance in PRPF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: ambiguous (0.531); Absent from gnomAD v4.1.

How common is PRPF3 p.Pro427Ser (c.1279C>T) in the general population?

PRPF3 p.Pro427Ser (c.1279C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPF3 p.Pro427Ser (c.1279C>T)?

AlphaMissense predicts ambiguous (score 0.531) — an in-silico prediction, not a clinical call.

PRPF3 p.Pro427Ser

c.1279C>T · rs2525187242 · VCV1720656

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.531 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.531	ambiguous
REVEL	0.799	moderately pathogenic-leaning
SaProt	LLR -5.66	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.55	unconstrained · MANE · 13 kb · p 7e-23 · regional, not allelic
Overall
CADD	26.5	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.Pro427Ser
Coding: c.1279C>T
MANE Select: NM_004698
dbSNP: rs2525187242
Type: single nucleotide variant
Location: chr1:150340474 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 427: the 'mediates interaction with sart3' region

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

Similar variants

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
PRPF3 p.Gln445Arg 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-pro427ser (accessed [today's date]).

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