Is CFI p.Glu290Asp (c.870A>C) pathogenic?

CFI p.Glu290Asp (c.870A>C) is classified Conflicting classifications of pathogenicity in CFI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.8091); Very rare (popmax 0.000678%, nfe); Associated with CFI-related disorder.

What condition is associated with CFI p.Glu290Asp (c.870A>C)?

CFI p.Glu290Asp (c.870A>C) is associated with CFI-related disorder (ClinVar).

How common is CFI p.Glu290Asp (c.870A>C) in the general population?

CFI p.Glu290Asp (c.870A>C) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about CFI p.Glu290Asp (c.870A>C)?

AlphaMissense predicts likely pathogenic (score 0.8091) — an in-silico prediction, not a clinical call.

CFI p.Glu290Asp

c.870A>C · VCV3671522

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8091 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CFI-related disorder

Computational evidence

Protein change
AlphaMissense	0.8091	likely pathogenic
REVEL	0.766	pathogenic-leaning
SaProt	LLR -13.32	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.62	GERP -3.5
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	18.87	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 0.000678% European (non-Finnish) · 8/1,179,328 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,304 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.Glu290Asp
Coding: c.870A>C
MANE Select: NM_000204
Type: single nucleotide variant
Location: chr4:109760283 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 290: a binding site; a disulfide bond; the ldl-receptor class a 2 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.Glu290Ala Uncertain significance ★ same residue
CFI p.Glu290Gln 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-glu290asp (accessed [today's date]).

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