Is CCDC40 p.Val775Met (c.2323G>A) pathogenic?

CCDC40 p.Val775Met (c.2323G>A) is classified Benign/Likely benign in CCDC40 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.145); Common (popmax 21.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia 15.

What condition is associated with CCDC40 p.Val775Met (c.2323G>A)?

CCDC40 p.Val775Met (c.2323G>A) 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.

What do computational predictors say about CCDC40 p.Val775Met (c.2323G>A)?

AlphaMissense predicts likely benign (score 0.145) — an in-silico prediction, not a clinical call.

CCDC40 p.Val775Met

Q: How common is CCDC40 p.Val775Met (c.2323G>A) in the general population?

CCDC40 p.Val775Met (c.2323G>A) is common (popmax 21.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2323G>A · rs60684213 · VCV162851

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.145 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 21.1%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

primary ciliary dyskinesia 15

Computational evidence

Protein change
AlphaMissense	0.145	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 1.4, phastCons 0.6
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.29 · regional, not allelic
Overall
CADD	16.69	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 21.1% African / African-American · 15,855/75,016 alleles

Filtering AF 20.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 20.7%

Overall 8.62% 139,068/1,614,060 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	21.1%	5
Middle Eastern	13%	8
Finnishnot grpmax-eligible	11.4%	9
Ashkenazi Jewishnot grpmax-eligible	10.5%	10
South Asian	9.82%	10
Remaining individualsnot grpmax-eligible	8.91%	11
European (non-Finnish)	7.96%	13
Amishnot grpmax-eligible	7.13%	14
Admixed American	5.8%	17
East Asian	0.0401%	2,493

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.Val775Met
Coding: c.2323G>A
MANE Select: NM_017950
dbSNP: rs60684213
Type: single nucleotide variant
Location: chr17:80086090 (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.Val775= 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-val775met (accessed [today's date]).

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