Is PRPF31 p.Pro88Arg (c.263C>G) pathogenic?

PRPF31 p.Pro88Arg (c.263C>G) is classified Uncertain significance in PRPF31 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely pathogenic (0.816); Very rare (popmax 0.00134%, afr).

How common is PRPF31 p.Pro88Arg (c.263C>G) in the general population?

PRPF31 p.Pro88Arg (c.263C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PRPF31 p.Pro88Arg (c.263C>G)?

AlphaMissense predicts likely pathogenic (score 0.816) — an in-silico prediction, not a clinical call.

PRPF31 p.Pro88Arg

c.263C>G · VCV4943792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.816	likely pathogenic
REVEL	0.721	pathogenic-leaning
SaProt	LLR -11.34	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 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 5,159 bp · p 4e-06 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 0.00134% African / African-American · 1/74,894 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,612,324 alleles · very rare exomes 2/1,460,106 · genomes 2/152,218 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,894
European (non-Finnish)	0.000254%	393,125

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRPF31
Protein: p.Pro88Arg
Coding: c.263C>G
MANE Select: NM_015629
Type: single nucleotide variant
Location: chr19:54121884 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB

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

Similar variants

PRPF31 c.1073+1G>A Pathogenic ★★ same type
PRPF31 c.1074-1G>C Likely pathogenic ★★ same type
PRPF31 c.1074-2A>G Pathogenic ★★ same type
PRPF31 c.1074-2A>T Pathogenic ★★ same type
PRPF31 c.1146+2T>C Pathogenic ★★ same type
PRPF31 c.1146+5G>T Likely pathogenic ★★ same type
PRPF31 c.1374+654C>G Pathogenic ★★ same type
PRPF31 c.178-2A>G Pathogenic ★★ 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/prpf31-p-pro88arg (accessed [today's date]).

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