Is PRPF40A p.Phe482Val (c.1444T>G) pathogenic?

PRPF40A p.Phe482Val (c.1444T>G) is classified Uncertain significance in PRPF40A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.000424%, nfe).

How common is PRPF40A p.Phe482Val (c.1444T>G) in the general population?

PRPF40A p.Phe482Val (c.1444T>G) is very rare (popmax 0.000424%, nfe) (gnomAD).

PRPF40A p.Phe482Val

c.1444T>G · VCV4572382

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.447	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,248 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,612,420 alleles · very rare exomes 2/1,460,228 · genomes 3/152,192 · joint denominator

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: PRPF40A
Protein: p.Phe482Val
Coding: c.1444T>G
MANE Select: NM_001365597
Type: single nucleotide variant
Location: chr2:152672511 (GRCh38)
Gene constraint: LOEUF 0.44 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.14 · 12 PDB
Residue 482: the ff 2 domain

Full PRPF40A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPF40A p.Ser646= Benign ★★ same type
PRPF40A p.Ala150Val Uncertain significance ★ same type
PRPF40A p.Ala225Thr Uncertain significance ★ same type
PRPF40A p.Ala297Gly Uncertain significance ★ same type
PRPF40A p.Ala298Val Uncertain significance ★ same type
PRPF40A p.Ala306Gly Uncertain significance ★ same type
PRPF40A p.Ala355Val Uncertain significance ★ same type
PRPF40A p.Ala445Val 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/prpf40a-p-phe482val (accessed [today's date]).

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