Is CFI p.Gly362Ala (c.1085G>C) pathogenic?

CFI p.Gly362Ala (c.1085G>C) is classified Uncertain significance in CFI (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-11). AlphaMissense: likely benign (0.1322); Very rare (popmax 0.00271%, nfe); Associated with CFI-related disorder.

What condition is associated with CFI p.Gly362Ala (c.1085G>C)?

CFI p.Gly362Ala (c.1085G>C) is associated with CFI-related disorder (ClinVar).

How common is CFI p.Gly362Ala (c.1085G>C) in the general population?

CFI p.Gly362Ala (c.1085G>C) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about CFI p.Gly362Ala (c.1085G>C)?

AlphaMissense predicts likely benign (score 0.1322) — an in-silico prediction, not a clinical call.

CFI p.Gly362Ala

c.1085G>C · rs200619905 · VCV2415819

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1322 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.1322	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -14.27	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -3.1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	2.725	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

Grpmax group 0.00271% European (non-Finnish) · 32/1,180,026 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,614,026 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00271%	36,876
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Gly362Ala
Coding: c.1085G>C
MANE Select: NM_000204
dbSNP: rs200619905
Type: single nucleotide variant
Location: chr4:109749281 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 362: a disulfide bond; the peptidase s1 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.Gly362Arg Uncertain significance ★ ⚠ same residue
CFI p.Gly362Glu 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

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-gly362ala (accessed [today's date]).

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