Is CCDC40 p.Asp410Asn (c.1228G>A) pathogenic?

CCDC40 p.Asp410Asn (c.1228G>A) is classified Uncertain significance in CCDC40 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-10). AlphaMissense: likely benign (0.2078); Ultra-rare (popmax 0.0627%, afr); Associated with primary ciliary dyskinesia.

What condition is associated with CCDC40 p.Asp410Asn (c.1228G>A)?

CCDC40 p.Asp410Asn (c.1228G>A) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 15 (ClinVar).

How common is CCDC40 p.Asp410Asn (c.1228G>A) in the general population?

CCDC40 p.Asp410Asn (c.1228G>A) is ultra-rare (popmax 0.0627%, afr) (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 CCDC40 p.Asp410Asn (c.1228G>A)?

AlphaMissense predicts likely benign (score 0.2078) — an in-silico prediction, not a clinical call.

CCDC40 p.Asp410Asn

c.1228G>A · rs370948871 · VCV1061235

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.2078	likely benign
REVEL	0.313	indeterminate
SaProt	LLR -5.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0627% African / African-American · 47/74,936 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00415% 67/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0627%	1,594
Admixed American	0.0233%	4,286
Remaining individualsnot grpmax-eligible	0.0032%	31,245
European (non-Finnish)	0.000339%	295,000

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.Asp410Asn
Coding: c.1228G>A
MANE Select: NM_017950
dbSNP: rs370948871
Type: single nucleotide variant
Location: chr17:80058562 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 15

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

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
CCDC40 p.Arg301Ter 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-asp410asn (accessed [today's date]).

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