Is PRPF31 p.Pro83Ala (c.247C>G) pathogenic?

PRPF31 p.Pro83Ala (c.247C>G) is classified Uncertain significance in PRPF31 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-19). AlphaMissense: likely pathogenic (0.685); Very rare (popmax 0.0017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PRPF31 p.Pro83Ala (c.247C>G)?

PRPF31 p.Pro83Ala (c.247C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PRPF31 p.Pro83Ala (c.247C>G) in the general population?

PRPF31 p.Pro83Ala (c.247C>G) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about PRPF31 p.Pro83Ala (c.247C>G)?

AlphaMissense predicts likely pathogenic (score 0.685) — an in-silico prediction, not a clinical call.

PRPF31 p.Pro83Ala

c.247C>G · rs747554145 · VCV1362598

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.685 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.685	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 5,159 bp · p 4e-06 · regional, not allelic
Overall
CADD	23.6	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 0.0017% European (non-Finnish) · 20/1,178,916 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.0013% 21/1,611,384 alleles · very rare exomes 21/1,459,052 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0017%	58,946
African / African-American	0.00133%	75,006

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.Pro83Ala
Coding: c.247C>G
MANE Select: NM_015629
dbSNP: rs747554145
Type: single nucleotide variant
Location: chr19:54121868 (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

Disease context

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

Similar variants

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
PRPF31 p.Asn218Asp Uncertain significance ★★ ⚠ same condition
PRPF31 p.Asn240His Uncertain significance ★★ ⚠ same condition
PRPF31 p.Asp42Glu 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-pro83ala (accessed [today's date]).

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