Is FANCF p.Arg42fs (c.123dup) pathogenic?

FANCF p.Arg42fs (c.123dup) is classified Pathogenic in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2019-01-23). Absent from gnomAD; Associated with Fanconi anemia.

What condition is associated with FANCF p.Arg42fs (c.123dup)?

FANCF p.Arg42fs (c.123dup) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Arg42fs (c.123dup) in the general population?

FANCF p.Arg42fs (c.123dup) is absent from gnomAD (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

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

FANCF p.Arg42fs

c.123dup · rs1858636931 · VCV847349

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (1 of 1) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.3	GERP 1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FANCF
Protein: p.Arg42fs
Coding: c.123dup
MANE Select: NM_022725
dbSNP: rs1858636931
Type: Duplication
Location: chr11:22625687 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 42: 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.Arg42His Uncertain significance ★ ⚠ same residue
FANCF p.Arg42= Likely benign ★ same residue
FANCF p.Gln130fs Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Thr30fs Pathogenic ★ same condition
FANCF p.Tyr109Ter Pathogenic ★ same condition
FANCF p.Arg138_Arg139insLeuAlaArg Uncertain significance ★ same condition
FANCF p.Arg33dup Uncertain significance ★ same condition
FANCF p.Ala180fs 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/fancf-p-arg42fs (accessed [today's date]).

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