Is PRPF31 p.Pro336Arg (c.1007C>G) pathogenic?

PRPF31 p.Pro336Arg (c.1007C>G) is classified Uncertain significance in PRPF31 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-10-13). AlphaMissense: likely pathogenic (0.9596); Absent from gnomAD v4.1; Associated with retinitis pigmentosa 11.

What condition is associated with PRPF31 p.Pro336Arg (c.1007C>G)?

PRPF31 p.Pro336Arg (c.1007C>G) is associated with retinitis pigmentosa 11 (ClinVar).

How common is PRPF31 p.Pro336Arg (c.1007C>G) in the general population?

PRPF31 p.Pro336Arg (c.1007C>G) 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 PRPF31 p.Pro336Arg (c.1007C>G)?

AlphaMissense predicts likely pathogenic (score 0.9596) — an in-silico prediction, not a clinical call.

PRPF31 p.Pro336Arg

c.1007C>G · rs1555794210 · VCV522515

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9596 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

retinitis pigmentosa 11

Computational evidence

Protein change
AlphaMissense	0.9596	likely pathogenic
REVEL	0.657	pathogenic-leaning
SaProt	LLR -11.28	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 7.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 7,893 bp · p 1.4e-13 · regional, not allelic
Overall
CADD	25.7	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.

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: PRPF31
Protein: p.Pro336Arg
Coding: c.1007C>G
MANE Select: NM_015629
dbSNP: rs1555794210
Type: single nucleotide variant
Location: chr19:54128134 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB
Residue 336: the 'disordered' region

Full PRPF31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

retinitis pigmentosa 11 — 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

PRPF31 c.1074-1G>C Likely pathogenic ★★ same condition
PRPF31 c.1146+5G>T Likely pathogenic ★★ same condition
PRPF31 c.1374+654C>G Pathogenic ★★ same condition
PRPF31 c.238+1G>A Pathogenic ★★ same condition
PRPF31 c.239-1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPF31 c.239-1G>T Pathogenic/Likely pathogenic ★★ same condition
PRPF31 c.322+1G>A Pathogenic/Likely pathogenic ★★ same condition
PRPF31 c.420+1G>A 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/prpf31-p-pro336arg (accessed [today's date]).

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