CCDC30

Chr 1AR

coiled-coil domain containing 30

Also known as: PFD6L, PFDN6L

NCBI Gene: 728621 ENSG00000186409 UniProt: Q5VVM6 OMIM: 613807

CCDC30 encodes a coiled-coil domain-containing protein that is essential for proper ciliary structure and function. Mutations cause primary ciliary dyskinesia-14, an autosomal recessive disorder characterized by chronic respiratory tract infections, bronchiectasis, and situs inversus due to defective motile cilia. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from OMIM

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 0.932 OMIM phenotypes

Clinical Summary— CCDC30

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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

4 unique Pathogenic / Likely Pathogenic· 216 VUS of 392 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.93LOEUF

pLI 0.000

Z-score 1.96

OE 0.70 (0.53–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.91Z-score

OE missense 0.87 (0.79–0.95)

318 obs / 366.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.70 (0.53–0.93)

0≤0.351.4

Missense OE?0.87 (0.79–0.95)

0≤0.61.4

Synonymous OE?0.87

0≤1.21.6

LoF obs/exp: 34 / 48.8Missense obs/exp: 318 / 366.8Syn Z: 1.12

This gene — mechanism propensity

0.77top 25%

GOF

0.6931th %ile

LOF

0.2679th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction 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

392 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic3

VUS216

Likely Benign138

Benign9

Conflicting4

Pathogenic

Likely Pathogenic

216

VUS

138

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	1	2	0	0	3
VUS	18	196	1	1	216
Likely Benign	0	7	27	104	138
Benign	0	0	4	5	9
Conflicting	—				4
Total	19	206	32	110	371

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

View in ClinVar →

12 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap CCDC30 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →