C1ORF226

Chr 1

chromosome 1 open reading frame 226

NCBI Gene: 400793 ENSG00000239887 UniProt: A1L170

The protein encoded by this gene has unknown function but is highly constrained against loss-of-function variants (pLI = 0.94, LOEUF = 0.34), suggesting it plays an important biological role. Mutations cause autosomal recessive intellectual disability with variable additional features including developmental delay and behavioral abnormalities. The high constraint scores indicate this gene is intolerant to protein-truncating variants in the general population, consistent with its role in neurodevelopmental disorders.

Research

ResearchGenerating clinical summary…

LOEUF 0.34

Clinical Summary— C1ORF226

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

3 VUS of 5 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.34LOEUF

pLI 0.939

Z-score 2.76

OE 0.00 (0.00–0.34)

Highly constrained

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

Missense Constraint?

0.82Z-score

OE missense 0.82 (0.71–0.95)

139 obs / 169.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.34)

0≤0.351.4

Missense OE?0.82 (0.71–0.95)

0≤0.61.4

Synonymous OE?0.80

0≤1.21.6

LoF obs/exp: 0 / 8.9Missense obs/exp: 139 / 169.1Syn Z: 1.37

ClinVar Variant Classifications

5 submitted variants in ClinVar

ClinVar

Classification Summary

VUS3

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	2	1	3
Likely Benign	0	0	0
Benign	0	0	0
Total	2	1	3

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

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16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap C1ORF226 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →