Is PRPF4 p.Pro314Arg (c.941C>G) pathogenic?

PRPF4 p.Pro314Arg (c.941C>G) is classified Uncertain significance in PRPF4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely pathogenic (0.9612); Absent from gnomAD v4.1.

How common is PRPF4 p.Pro314Arg (c.941C>G) in the general population?

PRPF4 p.Pro314Arg (c.941C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPF4 p.Pro314Arg (c.941C>G)?

AlphaMissense predicts likely pathogenic (score 0.9612) — an in-silico prediction, not a clinical call.

PRPF4 p.Pro314Arg

c.941C>G · rs587777599 · VCV2968717

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9612 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9612	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -15.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 16 kb · p 6e-12 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P315R vs ClinVar P314R) — verify the residue.

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: PRPF4
Protein: p.Pro314Arg
Coding: c.941C>G
MANE Select: NM_001244926
dbSNP: rs587777599
Type: single nucleotide variant
Location: chr9:113288183 (GRCh38)
Gene constraint: LOEUF 0.294 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.33 · 25 PDB
Residue 315 UniProt numbering: a UniProt-annotated variant site (in rp70)

Full PRPF4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF4 p.Pro314Leu Likely pathogenic ★★ same residue
PRPF4 p.Pro314Thr Uncertain significance ★ ⚠ same residue
PRPF4 c.654+4A>T Uncertain significance ★★ same type
PRPF4 p.Ala195Thr Uncertain significance ★★ ⚠ same type
PRPF4 p.Ala299Val Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg206Ser Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg438Trp Uncertain significance ★★ ⚠ same type
PRPF4 p.Arg439Cys 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/prpf4-p-pro314arg (accessed [today's date]).

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