Is FANCI p.Ile432Phe (c.1294A>T) pathogenic?

FANCI p.Ile432Phe (c.1294A>T) is classified Uncertain significance in FANCI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1537); Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCI p.Ile432Phe (c.1294A>T)?

FANCI p.Ile432Phe (c.1294A>T) is associated with Fanconi anemia (ClinVar).

How common is FANCI p.Ile432Phe (c.1294A>T) in the general population?

FANCI p.Ile432Phe (c.1294A>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 FANCI p.Ile432Phe (c.1294A>T)?

AlphaMissense predicts likely benign (score 0.1537) — an in-silico prediction, not a clinical call.

FANCI p.Ile432Phe

c.1294A>T · VCV4702168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1537 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.1537	likely benign
REVEL	0.343	indeterminate
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.50	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.44	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.1	GERP -2.6, phastCons 0.99
Regional constraint	o/e 1.12	unconstrained · MANE · 40 kb · p 0.00011 · regional, not allelic
Overall
CADD	18.37	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: FANCI
Protein: p.Ile432Phe
Coding: c.1294A>T
MANE Select: NM_001113378
Type: single nucleotide variant
Location: chr15:89278687 (GRCh38)
Gene constraint: LOEUF 0.959 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.61 · 8 PDB
Residue 432: an α-helix

Full FANCI 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

FANCI p.Ile432Val Uncertain significance ★★ ⚠ same residue
FANCI c.1512+1G>A Likely pathogenic ★★ same condition
FANCI c.158-2A>G Pathogenic/Likely pathogenic ★★ same condition
FANCI c.1584-1G>C Likely pathogenic ★★ same condition
FANCI c.1698+1G>A Likely pathogenic ★★ same condition
FANCI c.1891-2A>G Likely pathogenic ★★ same condition
FANCI c.2291+2T>A Likely pathogenic ★★ same condition
FANCI c.2292-1G>T Likely pathogenic ★★ 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/fanci-p-ile432phe (accessed [today's date]).

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