Is CFI p.Phe139Leu (c.417C>A) pathogenic?

CFI p.Phe139Leu (c.417C>A) is classified Uncertain significance in CFI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). AlphaMissense: likely pathogenic (0.7932); Absent from gnomAD v4.1.

How common is CFI p.Phe139Leu (c.417C>A) in the general population?

CFI p.Phe139Leu (c.417C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CFI p.Phe139Leu (c.417C>A)?

AlphaMissense predicts likely pathogenic (score 0.7932) — an in-silico prediction, not a clinical call.

CFI p.Phe139Leu

c.417C>A · rs2545450217 · VCV2772520

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7932 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7932	likely pathogenic
REVEL	0.236	benign-leaning
SaProt	LLR -5.40	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.96, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 61 kb · p 0.95 · regional, not allelic
Overall
CADD	16.48	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.Phe139Leu
Coding: c.417C>A
MANE Select: NM_000204
dbSNP: rs2545450217
Type: single nucleotide variant
Location: chr4:109764602 (GRCh38)
Gene constraint: LOEUF 1.076 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.50 · 2 PDB
Residue 139: a disulfide bond; the srcr domain; a β-strand

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

Similar variants

CFI p.Phe139Val Uncertain significance ★★ ⚠ same residue
CFI p.Phe139Ser Uncertain significance ★ ⚠ 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-phe139leu (accessed [today's date]).

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