Is CFAP74 p.Leu975fs (c.2924del) pathogenic?

CFAP74 p.Leu975fs (c.2924del) is classified Likely pathogenic in CFAP74 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-01). Ultra-rare (popmax 0.0702%, sas); Associated with ciliary dyskinesia, primary, 49, without situs inversus.

What condition is associated with CFAP74 p.Leu975fs (c.2924del)?

CFAP74 p.Leu975fs (c.2924del) is associated with ciliary dyskinesia, primary, 49, without situs inversus (ClinVar).

How common is CFAP74 p.Leu975fs (c.2924del) in the general population?

CFAP74 p.Leu975fs (c.2924del) is ultra-rare (popmax 0.0702%, sas) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CFAP74 p.Leu975fs

c.2924del · VCV3340495

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0702%, sas)

Conditions

ciliary dyskinesia, primary, 49, without situs inversus

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 25 of 39
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.047	GERP -2.3, phastCons 0.89
Overall
CADD	25.8	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 0.0702% South Asian · 59/84,068 alleles

Filtering AF 0.0558% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.00553% 85/1,536,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0702%	1,425
Remaining individualsnot grpmax-eligible	0.00833%	12,004
European (non-Finnish)	0.00183%	54,615

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: CFAP74
Protein: p.Leu975fs
Coding: c.2924del
MANE Select: NM_001304360
Type: Deletion
Location: chr1:1938942 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.38

Full CFAP74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ciliary dyskinesia, primary, 49, without situs inversus — 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

CFAP74 p.Leu572fs Likely pathogenic ★ same condition
CFAP74 p.Met278fs Likely pathogenic ★ same condition
CFAP74 p.Gln303fs Pathogenic same condition
CFAP74 p.Phe1461fs Pathogenic/Likely pathogenic ★★ same condition
CFAP74 p.Arg280Ter Likely pathogenic ★ same condition
CFAP74 p.Gly570fs Likely pathogenic ★ same condition
CFAP74 p.Val768Gly Uncertain significance ★ ⚠ same condition
CFAP74 p.Arg218Trp 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/cfap74-p-leu975fs (accessed [today's date]).

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