Is CFI p.Arg502Leu (c.1505G>T) pathogenic?

CFI p.Arg502Leu (c.1505G>T) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.6609); Absent from gnomAD v4.1; Associated with CFI-related disorder.

What condition is associated with CFI p.Arg502Leu (c.1505G>T)?

CFI p.Arg502Leu (c.1505G>T) is associated with CFI-related disorder (ClinVar).

How common is CFI p.Arg502Leu (c.1505G>T) in the general population?

CFI p.Arg502Leu (c.1505G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFI p.Arg502Leu (c.1505G>T)?

AlphaMissense predicts likely pathogenic (score 0.6609) — an in-silico prediction, not a clinical call.

CFI p.Arg502Leu

c.1505G>T · VCV4280539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6609 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.6609	likely pathogenic
REVEL	0.673	pathogenic-leaning
SaProt	LLR -7.09	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

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.Arg502Leu
Coding: c.1505G>T
MANE Select: NM_000204
Type: single nucleotide variant
Location: chr4:109742520 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 502: a disulfide bond; the peptidase s1 domain

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.Arg502Cys Uncertain significance ★★ ⚠ same residue
CFI p.Arg502Gly Uncertain significance ★ ⚠ same residue
CFI p.Arg502His 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

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-arg502leu (accessed [today's date]).

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