Is CCDC39 p.Tyr616= (c.1848T>C) pathogenic?

CCDC39 p.Tyr616= (c.1848T>C) is classified Likely benign in CCDC39 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-01-27). Rare (popmax 0.122%, sas); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Tyr616= (c.1848T>C)?

CCDC39 p.Tyr616= (c.1848T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Tyr616= (c.1848T>C) in the general population?

CCDC39 p.Tyr616= (c.1848T>C) is rare (popmax 0.122%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CCDC39 p.Tyr616=

c.1848T>C · rs774871939 · VCV704324

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.122%, sas)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.39	GERP -4.7
Overall
CADD	0.755	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.122% South Asian · 107/87,438 alleles

Filtering AF 0.104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0965%

Overall 0.0072% 115/1,597,300 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.122%	817
Remaining individualsnot grpmax-eligible	0.00486%	20,584
Finnishnot grpmax-eligible	0.00472%	21,185
East Asian	0.00225%	44,406
African / African-American	0.00135%	74,316

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CCDC39
Protein: p.Tyr616=
Coding: c.1848T>C
MANE Select: NM_181426
dbSNP: rs774871939
Type: single nucleotide variant
Location: chr3:180642019 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.23 · 1 PDB

Full CCDC39 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

CCDC39 c.1034+2T>A Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1167+1261A>G Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.1362+1G>A Likely pathogenic ★★ same condition
CCDC39 c.1999-2A>T Pathogenic/Likely pathogenic ★★ same condition
CCDC39 c.210+2T>C Pathogenic ★★ same condition
CCDC39 c.357+1G>C Pathogenic ★★ same condition
CCDC39 c.516+1G>A Likely pathogenic ★★ same condition
CCDC39 c.610-2A>G Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ccdc39-p-tyr616 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown