Is PRPF3 p.Ile183Val (c.547A>G) pathogenic?

PRPF3 p.Ile183Val (c.547A>G) is classified Uncertain significance in PRPF3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0544); Very rare (popmax 0.00267%, afr).

How common is PRPF3 p.Ile183Val (c.547A>G) in the general population?

PRPF3 p.Ile183Val (c.547A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PRPF3 p.Ile183Val (c.547A>G)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

PRPF3 p.Ile183Val

c.547A>G · VCV4748330

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -5.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 331 bp · p 0.14 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00267% African / African-American · 2/74,910 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,854 alleles · very rare exomes 6/1,461,696 · genomes 2/152,158 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,455
European (non-Finnish)	0.000508%	196,669

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: PRPF3
Protein: p.Ile183Val
Coding: c.547A>G
MANE Select: NM_004698
Type: single nucleotide variant
Location: chr1:150333018 (GRCh38)
Gene constraint: LOEUF 0.087 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 30 PDB
Residue 183: the 'disordered' region

Full PRPF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF3 p.Arg449Gly Pathogenic/Likely pathogenic ★★ same type
PRPF3 p.His499Pro Pathogenic ★★ same type
PRPF3 p.Pro493Ser Pathogenic ★★ same type
PRPF3 p.Thr494Met Pathogenic ★★ same type
PRPF3 p.Ala489Pro Uncertain significance ★★ ⚠ same type
PRPF3 p.Arg641Gln Uncertain significance ★★ ⚠ same type
PRPF3 p.Asp43Gly Uncertain significance ★★ ⚠ same type
PRPF3 p.Gln445Arg 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/prpf3-p-ile183val (accessed [today's date]).

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