Is CFAP300 p.Lys68fs (c.201_202insCC) pathogenic?

CFAP300 p.Lys68fs (c.201202insCC) is classified Pathogenic in CFAP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-05). Ultra-rare (popmax 0.0106%, nfe); Associated with ciliary dyskinesia, primary, 38.

What condition is associated with CFAP300 p.Lys68fs (c.201_202insCC)?

CFAP300 p.Lys68fs (c.201_202insCC) is associated with ciliary dyskinesia, primary, 38 (ClinVar).

How common is CFAP300 p.Lys68fs (c.201_202insCC) in the general population?

CFAP300 p.Lys68fs (c.201_202insCC) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CFAP300 p.Lys68fs

c.201_202insCC · VCV4852587

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Conditions

ciliary dyskinesia, primary, 38

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 123/1,161,972 alleles

Filtering AF 0.00906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00849%

Overall 0.0289% 456/1,576,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.505%	198
Remaining individualsnot grpmax-eligible	0.0197%	5,072
European (non-Finnish)grpmax	0.0106%	9,447
Admixed American	0.00185%	54,006

Finnish 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: CFAP300
Protein: p.Lys68fs
Coding: c.201_202insCC
MANE Select: NM_032930
Type: Insertion
Location: chr11:102058887 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21
Residue 68: a UniProt-annotated variant site (in cild38; loss of ciliary axoneme inner dynein arm and outer dynein arm structures in patient respiratory epithelial cells)

Full CFAP300 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 38 — 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

CFAP300 p.Arg121Ter Pathogenic ★★ same condition
CFAP300 p.Arg144Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP300 p.Gln160Ter Pathogenic ★★ same condition
CFAP300 p.Gln52Ter Pathogenic ★★ same condition
CFAP300 p.His259Arg Pathogenic/Likely pathogenic ★★ same condition
CFAP300 p.Phe67fs Pathogenic ★★ same condition
CFAP300 c.110+16A>G Benign ★★ same condition
CFAP300 c.192+59A>C Benign ★★ 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/cfap300-p-lys68fs (accessed [today's date]).

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