Is FANCF p.Ile44Phe (c.130A>T) pathogenic?

FANCF p.Ile44Phe (c.130A>T) is classified Uncertain significance in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-08). AlphaMissense: ambiguous (0.5591); Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCF p.Ile44Phe (c.130A>T)?

FANCF p.Ile44Phe (c.130A>T) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Ile44Phe (c.130A>T) in the general population?

FANCF p.Ile44Phe (c.130A>T) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about FANCF p.Ile44Phe (c.130A>T)?

AlphaMissense predicts ambiguous (score 0.5591) — an in-silico prediction, not a clinical call.

FANCF p.Ile44Phe

c.130A>T · rs2133798589 · VCV2194907

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5591 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.5591	ambiguous
REVEL	0.083	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.34	GERP -3.7, phastCons 0.11
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	11.63	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: FANCF
Protein: p.Ile44Phe
Coding: c.130A>T
MANE Select: NM_022725
dbSNP: rs2133798589
Type: single nucleotide variant
Location: chr11:22625681 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 44: an α-helix

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

Disease context

Fanconi anemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCF p.Gln65Ter Likely pathogenic ★★ same condition
FANCF p.Glu220Ter Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Glu223Ter Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Met1Arg Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Ala124Ser Uncertain significance ★★ ⚠ same condition
FANCF p.Ala206Val Uncertain significance ★★ ⚠ same condition
FANCF p.Ala334Val Uncertain significance ★★ ⚠ same condition
FANCF p.Ala34Val 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/fancf-p-ile44phe (accessed [today's date]).

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