PRPF38A

Chr 1

pre-mRNA processing factor 38A

Also known as: PRP38A, Prp38

NCBI Gene: 84950 ENSG00000134748 OMIM: 617031

The PRPF38A protein is a component of the spliceosome that binds RNA and is involved in pre-mRNA splicing within the nucleoplasm. Mutations cause autosomal recessive retinitis pigmentosa, a progressive retinal degeneration leading to vision loss. The gene shows significant constraint against loss-of-function variants (LOEUF 0.408), indicating that complete loss of function is likely poorly tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.41

Clinical Summary— PRPF38A

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.77) — some intolerance to loss-of-function variants.

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ClinVar Variants

36 VUS of 50 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.41LOEUF

pLI 0.772

Z-score 3.61

OE 0.18 (0.09–0.41)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.11Z-score

OE missense 0.58 (0.49–0.68)

114 obs / 197.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.18 (0.09–0.41)

0≤0.351.4

Missense OE?0.58 (0.49–0.68)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 4 / 22.5Missense obs/exp: 114 / 197.4Syn Z: 0.19

This gene — mechanism propensity

0.3991th %ile

GOF

0.4282th %ile

LOF

0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.41

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

50 submitted variants in ClinVar

ClinVar

Classification Summary

VUS36

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	36	0	36
Likely Benign	0	1	1
Benign	0	0	0
Total	36	1	37

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

7 pathogenic / likely-pathogenic (of 10) ClinVar copy-number / structural variants overlap PRPF38A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →