Is CFI p.Arg345Ter (c.1033C>T) pathogenic?

CFI p.Arg345Ter (c.1033C>T) is classified Pathogenic in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-09). Very rare (popmax 0.0011%, sas).

How common is CFI p.Arg345Ter (c.1033C>T) in the general population?

CFI p.Arg345Ter (c.1033C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

CFI p.Arg345Ter

c.1033C>T · rs768411190 · VCV2902474

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 13
Splicing
SpliceAI	Δ0.34	donor loss, 11 bp away · masked 0 · deltas
Pangolin	Δ0.41	loss · gain 0.23 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.17	GERP -1.8
Overall
CADD	34.0	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 0.0011% South Asian · 1/91,060 alleles

Overall 6.85e-05% 1/1,460,272 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: CFI
Protein: p.Arg345Ter
Coding: c.1033C>T
MANE Select: NM_000204
dbSNP: rs768411190
Type: single nucleotide variant
Location: chr4:109749510 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 345: a disulfide bond; the peptidase s1 domain

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

Similar variants

CFI p.Arg345Gln Uncertain significance ★★ ⚠ same residue
CFI p.Arg345= Likely benign ★ same residue
CFI c.1429+1G>C Pathogenic/Likely pathogenic ★★ same type
CFI c.57+1G>C Likely pathogenic ★★ same type
CFI c.658+1G>A Likely pathogenic ★★ same type
CFI c.905-1G>C Likely pathogenic ★★ same type
CFI p.Ala258Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
CFI p.Arg187Ter Pathogenic/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-arg345ter (accessed [today's date]).

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