Is CFAP221 p.Arg36fs (c.106del) pathogenic?

CFAP221 p.Arg36fs (c.106del) is classified Pathogenic in CFAP221 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). Very rare (popmax 0.000262%, nfe).

How common is CFAP221 p.Arg36fs (c.106del) in the general population?

CFAP221 p.Arg36fs (c.106del) is very rare (popmax 0.000262%, nfe) (gnomAD).

CFAP221 p.Arg36fs

c.106del · VCV3773992

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000262%, nfe)

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 2 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.52	GERP -1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000262% European (non-Finnish) · 3/1,146,374 alleles

Filtering AF 7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000217% 3/1,382,732 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: CFAP221
Protein: p.Arg36fs
Coding: c.106del
MANE Select: NM_001271049
Type: Deletion
Location: chr2:119546231 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.53

Full CFAP221 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP221 p.Lys74fs Likely pathogenic ★ same type
CFAP221 p.Leu768fs Pathogenic/Likely pathogenic same type
CFAP221 p.Lys489fs 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/cfap221-p-arg36fs (accessed [today's date]).

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