Is PRPF31 p.Arg91Cys (c.271C>T) pathogenic?

PRPF31 p.Arg91Cys (c.271C>T) is classified Conflicting classifications of pathogenicity in PRPF31 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-11). AlphaMissense: ambiguous (0.539); Ultra-rare (popmax 0.0194%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRPF31 p.Arg91Cys (c.271C>T)?

PRPF31 p.Arg91Cys (c.271C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRPF31 p.Arg91Cys (c.271C>T) in the general population?

PRPF31 p.Arg91Cys (c.271C>T) is ultra-rare (popmax 0.0194%, nfe) (gnomAD).

What do computational predictors say about PRPF31 p.Arg91Cys (c.271C>T)?

AlphaMissense predicts ambiguous (score 0.539) — an in-silico prediction, not a clinical call.

PRPF31 p.Arg91Cys

c.271C>T · rs376072327 · VCV1508982

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.539 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0194%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.539	ambiguous
REVEL	0.438	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 5,159 bp · p 4e-06 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.0194% European (non-Finnish) · 229/1,179,504 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0165%

Overall 0.0157% 253/1,612,592 alleles · ultra-rare exomes 239/1,460,374 · genomes 14/152,218 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0194%	5,151
Admixed American	0.0167%	5,986
Remaining individualsnot grpmax-eligible	0.0112%	8,919
East Asian	0.00446%	22,418
African / African-American	0.00401%	24,961
South Asian	0.0022%	45,376

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.Arg91Cys
Coding: c.271C>T
MANE Select: NM_015629
dbSNP: rs376072327
Type: single nucleotide variant
Location: chr19:54121892 (GRCh38)
Gene constraint: LOEUF 0.347 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.69 · 30 PDB
Residue 91: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPF31 p.Arg91Gly Uncertain significance ★ ⚠ same residue
PRPF31 p.Arg91= Likely benign ★★ same residue
PRPF31 p.Arg91His Conflicting classifications of pathogenicity ★ ⚠ same residue
PRPF31 p.Ala235Gly Uncertain significance ★★ ⚠ same condition
PRPF31 p.Ala254Thr Uncertain significance ★★ same condition
PRPF31 p.Arg357Cys Uncertain significance ★★ ⚠ same condition
PRPF31 p.Arg372Gln Uncertain significance ★★ ⚠ same condition
PRPF31 p.Arg442His Uncertain significance ★★ ⚠ 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-arg91cys (accessed [today's date]).

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