Is CCDC40 p.Ala630= (c.1890T>G) pathogenic?

CCDC40 p.Ala630= (c.1890T>G) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Common (popmax 63.1%, mid) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Ala630= (c.1890T>G)?

CCDC40 p.Ala630= (c.1890T>G) 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.Ala630=

Q: How common is CCDC40 p.Ala630= (c.1890T>G) in the general population?

CCDC40 p.Ala630= (c.1890T>G) is common (popmax 63.1%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1890T>G · rs35578653 · VCV162850

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Common

common (popmax 63.1%, mid) — 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 -3.2	GERP -3.9
Overall
CADD	0.297	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 63.1% Middle Eastern · 3,825/6,060 alleles

Filtering AF 61.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.8%

Overall 50.9% 821,726/1,613,186 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	63.1%	2
Ashkenazi Jewishnot grpmax-eligible	60.4%	2
African / African-American	59.1%	2
Remaining individualsnot grpmax-eligible	52%	2
European (non-Finnish)	51.9%	2
Finnishnot grpmax-eligible	48.9%	2
South Asian	45.2%	2
Admixed American	40.1%	2
Amishnot grpmax-eligible	32.6%	3
East Asian	30.6%	3

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.Ala630=
Coding: c.1890T>G
MANE Select: NM_017950
dbSNP: rs35578653
Type: single nucleotide variant
Location: chr17:80081959 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.70 · 1 PDB

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.Ala630Val Benign/Likely benign ★★ 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
CCDC40 p.Arg1059Ter Pathogenic/Likely 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-ala630 (accessed [today's date]).

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