Is CFI p.Ile55Thr (c.164T>C) pathogenic?

CFI p.Ile55Thr (c.164T>C) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0976); Absent from gnomAD v4.1; Associated with CFI-related disorder.

What condition is associated with CFI p.Ile55Thr (c.164T>C)?

CFI p.Ile55Thr (c.164T>C) is associated with CFI-related disorder (ClinVar).

How common is CFI p.Ile55Thr (c.164T>C) in the general population?

CFI p.Ile55Thr (c.164T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFI p.Ile55Thr (c.164T>C)?

AlphaMissense predicts likely benign (score 0.0976) — an in-silico prediction, not a clinical call.

CFI p.Ile55Thr

c.164T>C · VCV4280498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0976 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.0976	likely benign
REVEL	0.394	indeterminate
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CFI
Protein: p.Ile55Thr
Coding: c.164T>C
MANE Select: NM_000204
Type: single nucleotide variant
Location: chr4:109766718 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 55: a disulfide bond; the kazal-like domain; a β-strand

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

Disease context

CFI-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFI p.Ile55Phe Uncertain significance ★★ ⚠ same residue
CFI p.Arg187Ter Pathogenic/Likely pathogenic ★★ same condition
CFI p.Arg474Ter Pathogenic/Likely pathogenic ★★ same condition
CFI p.Trp145Ter Pathogenic ★★ same condition
CFI p.Ala153Thr Uncertain significance ★★ ⚠ same condition
CFI p.Ala76Gly Uncertain significance ★★ ⚠ same condition
CFI p.Arg317Gln Uncertain significance ★★ ⚠ same condition
CFI p.Arg502Cys Uncertain significance ★★ ⚠ same condition

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-ile55thr (accessed [today's date]).

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