Is CCDC39 p.Leu206Phe (c.618G>C) pathogenic?

CCDC39 p.Leu206Phe (c.618G>C) is classified Uncertain significance in CCDC39 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.7109); Very rare (popmax 0.000848%, nfe); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC39 p.Leu206Phe (c.618G>C)?

CCDC39 p.Leu206Phe (c.618G>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is CCDC39 p.Leu206Phe (c.618G>C) in the general population?

CCDC39 p.Leu206Phe (c.618G>C) is very rare (popmax 0.000848%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

What do computational predictors say about CCDC39 p.Leu206Phe (c.618G>C)?

AlphaMissense predicts likely pathogenic (score 0.7109) — an in-silico prediction, not a clinical call.

CCDC39 p.Leu206Phe

c.618G>C · rs1048916587 · VCV950138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.7109	likely pathogenic · top 7% in CCDC39
REVEL	0.222	benign-leaning
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP 0.94, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 64 kb · p 0.72 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,152 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000685% 10/1,459,954 alleles · very rare

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.Leu206Phe
Coding: c.618G>C
MANE Select: NM_181426
dbSNP: rs1048916587
Type: single nucleotide variant
Location: chr3:180659572 (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-leu206phe (accessed [today's date]).

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