Is FANCF p.Ser18Ter (c.53C>G) pathogenic?

FANCF p.Ser18Ter (c.53C>G) is classified Pathogenic in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-12). Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCF p.Ser18Ter (c.53C>G)?

FANCF p.Ser18Ter (c.53C>G) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Ser18Ter (c.53C>G) in the general population?

FANCF p.Ser18Ter (c.53C>G) 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.

FANCF p.Ser18Ter

c.53C>G · VCV4713243

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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.Ser18Ter
Coding: c.53C>G
MANE Select: NM_022725
Type: single nucleotide variant
Location: chr11:22625758 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 18: 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.Ser18= Uncertain significance ★ same residue
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

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-ser18ter (accessed [today's date]).

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