CCDC14

Chr 3

coiled-coil domain containing 14

NCBI Gene: 64770 ENSG00000175455 UniProt: Q49A88 OMIM: 617147

The CCDC14 protein negatively regulates centriole duplication and controls the centrosomal localization of CEP63 and CDK2, with involvement in protein localization to the centrosome and ciliary basal body. Mutations cause autosomal recessive primary microcephaly with short stature. The gene shows no intolerance to loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Involved in protein localization to centrosome. Located in centriolar satellite and ciliary basal body. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.97

Clinical Summary— CCDC14

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

127 VUS of 161 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.97LOEUF

pLI 0.000

Z-score 1.69

OE 0.71 (0.53–0.97)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.78Z-score

OE missense 0.90 (0.83–0.97)

407 obs / 453.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.71 (0.53–0.97)

0≤0.351.4

Missense OE?0.90 (0.83–0.97)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 28 / 39.5Missense obs/exp: 407 / 453.9Syn Z: 1.31

This gene — mechanism propensity

0.6455th %ile

GOF

0.5367th %ile

LOF

0.4627th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

161 submitted variants in ClinVar

ClinVar

Classification Summary

VUS127

Likely Benign8

127

VUS

Likely Benign

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	110	17	127
Likely Benign	8	0	8
Benign	0	0	0
Total	118	17	135

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

View in ClinVar →

19 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap CCDC14 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →