Is CFI p.Lys99fs (c.296_297del) pathogenic?

CFI p.Lys99fs (c.296297del) is classified Pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-10). Absent from gnomAD.

How common is CFI p.Lys99fs (c.296_297del) in the general population?

CFI p.Lys99fs (c.296_297del) is absent from gnomAD (gnomAD).

CFI p.Lys99fs

c.296_297del · rs2545456303 · VCV2702129

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CFI
Protein: p.Lys99fs
Coding: c.296_297del
MANE Select: NM_000204
dbSNP: rs2545456303
Type: Deletion
Location: chr4:109766585 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 99: a disulfide bond; the kazal-like domain

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

Similar variants

CFI p.Asn549fs Likely pathogenic ★★ same type
CFI p.Glu434fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Gly263fs Pathogenic ★★ same type
CFI p.Leu484fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Lys89fs Pathogenic ★★ same type
CFI p.Met138fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Ala294del Uncertain significance ★★ same type
CFI c.329-8del Benign/Likely benign ★★ 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/cfi-p-lys99fs (accessed [today's date]).

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