Is CFI p.Pro64fs (c.188dup) pathogenic?

CFI p.Pro64fs (c.188dup) is classified Pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). Absent from gnomAD.

How common is CFI p.Pro64fs (c.188dup) in the general population?

CFI p.Pro64fs (c.188dup) is absent from gnomAD (gnomAD).

CFI p.Pro64fs

c.188dup · rs2545456988 · VCV2100265

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 0.43	GERP -3.7, phastCons 0.97

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.Pro64fs
Coding: c.188dup
MANE Select: NM_000204
dbSNP: rs2545456988
Type: Duplication
Location: chr4:109766693 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 64: a disulfide bond; the kazal-like domain; a UniProt-annotated variant site (in ahus3); an α-helix

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

Similar variants

CFI p.Pro64= Likely benign ★★ same residue
CFI p.Pro64Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
CFI p.Asn103fs Pathogenic/Likely pathogenic ★★ same type
CFI p.Gly574fs Uncertain significance ★★ same type
CFI c.329-14dup Benign/Likely benign ★★ same type
CFI p.Asp443fs Likely pathogenic ★ same type
CFI p.Ile368fs Pathogenic ★ same type
CFI p.Tyr390Ter Likely 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/cfi-p-pro64fs (accessed [today's date]).

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