Is CFAP298 p.Arg98Ter (c.292C>T) pathogenic?

CFAP298 p.Arg98Ter (c.292C>T) is classified Pathogenic/Likely pathogenic in CFAP298 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-13). Ultra-rare (popmax 0.0165%, mid); Associated with primary ciliary dyskinesia 26.

What condition is associated with CFAP298 p.Arg98Ter (c.292C>T)?

CFAP298 p.Arg98Ter (c.292C>T) is associated with primary ciliary dyskinesia 26 (ClinVar).

How common is CFAP298 p.Arg98Ter (c.292C>T) in the general population?

CFAP298 p.Arg98Ter (c.292C>T) is ultra-rare (popmax 0.0165%, mid) (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.Arg98Ter

c.292C>T · rs143740376 · VCV88689

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

primary ciliary dyskinesia 26

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.5, phastCons 1
Overall
CADD	39.0	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00713% 115/1,613,472 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0144%	6,943
Admixed American	0.01%	9,997
European (non-Finnish)	0.00788%	12,686
African / African-American	0.00401%	24,959
South Asian	0.0033%	30,337

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.Arg98Ter
Coding: c.292C>T
MANE Select: NM_021254
dbSNP: rs143740376
Type: single nucleotide variant
Location: chr21:32609853 (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.Arg98Gln Uncertain significance ★ ⚠ same residue
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
CFAP298 p.Gln241Ter Pathogenic ★ same condition
CFAP298 p.Gln190fs 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/cfap298-p-arg98ter (accessed [today's date]).

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