CWF19L1

Chr 10AR

CWF19 like cell cycle control factor 1

Also known as: C19L1, SCAR17, hDrn1

NCBI Gene: 55280 ENSG00000095485 UniProt: Q69YN2 OMIM: 616120

The protein is a member of the CWF19 family involved in pre-mRNA splicing. Mutations cause autosomal recessive spinocerebellar ataxia type 17, characterized by cerebellar ataxia and mild cognitive disability. This gene shows extreme intolerance to loss-of-function variants (pLI ~1.0), indicating it is highly constrained and essential for normal function.

OMIM ResearchSummary from RefSeq, OMIM

This gene encodes a member of the CWF19 protein family. Mutations in this gene have been associated with autosomal recessive spinocerebellar ataxia-17 and mild cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spinocerebellar ataxia, autosomal recessive 17MIM #616127

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · autosomal recessive cerebellar ataxia · AR · ClinGen 2025

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.15

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.15LOEUF

pLI 0.000

Z-score 0.89

OE 0.83 (0.61–1.15)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.10Z-score

OE missense 0.82 (0.73–0.91)

232 obs / 283.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.61–1.15)

0≤0.351.4

Missense OE?0.82 (0.73–0.91)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 26 / 31.4Missense obs/exp: 232 / 283.9Syn Z: 1.01

Background carrier burden — how many people carry a rare variant somewhere in CWF19L1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

630 rare PASS variants

Rare truncating (LoF)

1 in 1,300

124 rare PASS variants

Rare synonymous (reference)

1 in 220

218 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CWF19L1. 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 140	1 in 1,300
South Asian	~43k	1 in 130	1 in 1,000
Remaining (unassigned)	~30k	1 in 110	1 in 1,200
European (Finnish)	~27k	1 in 300	1 in 460
Admixed American	~22k	1 in 120	1 in 920
African / African American	~21k	1 in 120	1 in 640
East Asian	~20k	1 in 130	1 in 830
Ashkenazi Jewish	~13k	1 in 1,200	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 140	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): 13 of 14 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 14.? see exons ↓