Is CFAP298 p.Ile285fs (c.854_855del) pathogenic?

CFAP298 p.Ile285fs (c.854855del) is classified Uncertain significance in CFAP298 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). Very rare (popmax 0.00667%, amr).

How common is CFAP298 p.Ile285fs (c.854_855del) in the general population?

CFAP298 p.Ile285fs (c.854_855del) is very rare (popmax 0.00667%, amr) (gnomAD).

CFAP298 p.Ile285fs

c.854_855del · rs1165745783 · VCV947819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 2.7	GERP 1.5, 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 0.00667% Admixed American · 4/59,986 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00187% 30/1,607,592 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,997
European (non-Finnish)	0.00204%	48,931
Remaining individualsnot grpmax-eligible	0.00161%	62,270
South Asian	0.0011%	90,932

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.Ile285fs
Coding: c.854_855del
MANE Select: NM_021254
dbSNP: rs1165745783
Type: Deletion
Location: chr21:32601881 (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

Similar variants

CFAP298 p.Leu146fs Pathogenic/Likely pathogenic ★★ same type
CFAP298 p.Arg277fs Uncertain significance ★★ same type
CFAP298 c.535-13del Uncertain significance ★ same type
CFAP298 c.307+75del Likely benign ★ same type
CFAP298 c.375+20_375+26del Likely benign ★ same type
CFAP298 c.375+54del Benign ★ same type
CFAP298 p.Ala263_Tyr264insTer Pathogenic same type

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-ile285fs (accessed [today's date]).

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