Is CFAP298 p.Arg277fs (c.829del) pathogenic?

CFAP298 p.Arg277fs (c.829del) is classified Uncertain significance in CFAP298 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-23). Very rare (popmax 0.00017%, nfe); Associated with primary ciliary dyskinesia 26.

What condition is associated with CFAP298 p.Arg277fs (c.829del)?

CFAP298 p.Arg277fs (c.829del) is associated with primary ciliary dyskinesia 26 (ClinVar).

How common is CFAP298 p.Arg277fs (c.829del) in the general population?

CFAP298 p.Arg277fs (c.829del) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

CFAP298 p.Arg277fs

c.829del · rs2038749156 · VCV1025340

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

primary ciliary dyskinesia 26

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.7	GERP 1.5, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,076 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,460,762 alleles · very 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: CFAP298
Protein: p.Arg277fs
Coding: c.829del
MANE Select: NM_021254
dbSNP: rs2038749156
Type: Deletion
Location: chr21:32601907 (GRCh38)
Gene constraint: LOEUF 1.267 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.54

Full CFAP298 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia 26 — 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

CFAP298 p.Ala263_Tyr264insTer Pathogenic same condition
CFAP298 p.Arg98Ter Pathogenic/Likely pathogenic ★★ same condition
CFAP298 p.Gln190fs Pathogenic/Likely pathogenic ★★ same condition
CFAP298 p.Gln225Ter Pathogenic ★★ same condition
CFAP298 p.Asp141Gly Uncertain significance ★★ ⚠ same condition
CFAP298 c.308-16C>G Benign ★★ same condition
CFAP298 p.Ile184= Likely benign ★★ same condition
CFAP298 p.Val208Met Benign/Likely 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/cfap298-p-arg277fs (accessed [today's date]).

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