SNRPA1

Chr 15

small nuclear ribonucleoprotein polypeptide A'

Also known as: Lea1, U2A'

NCBI Gene: 6627 ENSG00000131876 UniProt: P09661

The SNRPA1 protein is a component of the U2 spliceosome that binds to U2 snRNA and is essential for pre-mRNA splicing. Mutations cause autosomal dominant connective tissue disease, and the gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.22), indicating that such variants are likely pathogenic.

ResearchSummary from RefSeq, UniProt

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome and spermatogenesis. Located in nuclear speck. Part of U2-type catalytic step 2 spliceosome and U2-type precatalytic spliceosome. Implicated in connective tissue disease. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.22LOEUF

pLI 0.990

Z-score 3.44

OE 0.00 (0.00–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.87Z-score

OE missense 0.55 (0.46–0.67)

75 obs / 136.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.22)

0≤0.351.4

Missense OE?0.55 (0.46–0.67)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 0 / 13.8Missense obs/exp: 75 / 136.5Syn Z: -0.68

Background carrier burden — how many people carry a rare variant somewhere in SNRPA1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 310

235 rare PASS variants

Rare truncating (LoF)

1 in 22,000

12 rare PASS variants

Rare synonymous (reference)

1 in 280

121 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SNRPA1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 400	1 in 31,000
South Asian	~43k	1 in 340	≈ 1 in 22,000
Remaining (unassigned)	~30k	1 in 190	≈ 1 in 15,000
European (Finnish)	~27k	1 in 840	none seen
Admixed American	~22k	1 in 250	≈ 1 in 7,600
African / African American	~21k	1 in 200	none seen
East Asian	~20k	1 in 360	≈ 1 in 16,000
Ashkenazi Jewish	~13k	≈ 1 in 3,300	none seen
Middle Eastern	~2,884	≈ 1 in 2,800	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 8 of 9 coding exons well covered in gnomAD exomes; exon 5 marginal. Genomes: all 9.? see exons ↓