Is CFAP300 p.Phe14Leu (c.40T>C) pathogenic?

CFAP300 p.Phe14Leu (c.40T>C) is classified Uncertain significance in CFAP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely pathogenic (0.9726); Ultra-rare (popmax 0.0171%, eas); Associated with ciliary dyskinesia, primary, 38.

What condition is associated with CFAP300 p.Phe14Leu (c.40T>C)?

CFAP300 p.Phe14Leu (c.40T>C) is associated with ciliary dyskinesia, primary, 38 (ClinVar).

How common is CFAP300 p.Phe14Leu (c.40T>C) in the general population?

CFAP300 p.Phe14Leu (c.40T>C) is ultra-rare (popmax 0.0171%, eas) (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 CFAP300 p.Phe14Leu (c.40T>C)?

AlphaMissense predicts likely pathogenic (score 0.9726) — an in-silico prediction, not a clinical call.

CFAP300 p.Phe14Leu

c.40T>C · VCV3598846

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9726 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ciliary dyskinesia, primary, 38

Computational evidence

Protein change
AlphaMissense	0.9726	likely pathogenic · top 3% in CFAP300
REVEL	0.472	indeterminate
SaProt	LLR -12.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 36 kb · p 0.034 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0171% East Asian · 7/40,900 alleles

Filtering AF 0.00799% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.000456% 7/1,535,986 alleles · ultra-rare

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.Phe14Leu
Coding: c.40T>C
MANE Select: NM_032930
Type: single nucleotide variant
Location: chr11:102047510 (GRCh38)
Gene constraint: LOEUF 1.386 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.21

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.Phe14Cys Uncertain significance ★ ⚠ same residue
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 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-phe14leu (accessed [today's date]).

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