Is CCDC40 p.Val69= (c.207G>C) pathogenic?

CCDC40 p.Val69= (c.207G>C) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 99.4%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Val69= (c.207G>C)?

CCDC40 p.Val69= (c.207G>C) is associated with primary ciliary dyskinesia 15, primary ciliary dyskinesia (ClinVar).

How is Primary ciliary dyskinesia inherited?

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

CCDC40 p.Val69=

Q: How common is CCDC40 p.Val69= (c.207G>C) in the general population?

CCDC40 p.Val69= (c.207G>C) is common (popmax 99.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.207G>C · rs2289527 · VCV166807

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 99.4%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.6
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 99.4% African / African-American · 74,418/74,880 alleles

Filtering AF 98.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.8%

Overall 98.2% 1,584,480/1,613,522 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	100%	1
African / African-Americangrpmax	99.4%	1
Middle Eastern	99.2%	1
European (non-Finnish)	99.1%	1
Ashkenazi Jewishnot grpmax-eligible	98.3%	1
Remaining individualsnot grpmax-eligible	97.9%	1
Finnishnot grpmax-eligible	97.9%	1
Admixed American	97.4%	1
South Asian	91.5%	1
East Asian	89%	1

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC40
Protein: p.Val69=
Coding: c.207G>C
MANE Select: NM_017950
dbSNP: rs2289527
Type: single nucleotide variant
Location: chr17:80039925 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 1 PDB
Residue 69: the 'disordered' region

Full CCDC40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

CCDC40 p.Val69Glu Uncertain significance ★ ⚠ same residue
CCDC40 p.Val69Gly Uncertain significance ★ ⚠ same residue
CCDC40 c.1159+1G>A Likely pathogenic ★★ same condition
CCDC40 c.1989+1G>A Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.2712-1G>T Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.855+1G>A Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.940-1G>C Pathogenic/Likely pathogenic ★★ same condition
CCDC40 c.940-2A>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/ccdc40-p-val69 (accessed [today's date]).

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