Is FANCF p.Lys291= (c.873A>G) pathogenic?

FANCF p.Lys291= (c.873A>G) is classified Conflicting classifications of pathogenicity in FANCF (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-25). Rare (popmax 0.23%, mid); Associated with Fanconi anemia.

What condition is associated with FANCF p.Lys291= (c.873A>G)?

FANCF p.Lys291= (c.873A>G) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Lys291= (c.873A>G) in the general population?

FANCF p.Lys291= (c.873A>G) is rare (popmax 0.23%, mid) (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.Lys291=

c.873A>G · rs757578045 · VCV695885

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.23%, mid)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.97	GERP -3.6
Overall
CADD	6.014	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.23% Middle Eastern · 14/6,084 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.00632% 102/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.23%	435
Admixed American	0.0317%	3,158
Remaining individualsnot grpmax-eligible	0.0256%	3,905
African / African-American	0.012%	8,324
South Asian	0.00549%	18,218
European (non-Finnish)	0.0033%	30,257

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FANCF
Protein: p.Lys291=
Coding: c.873A>G
MANE Select: NM_022725
dbSNP: rs757578045
Type: single nucleotide variant
Location: chr11:22624938 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 291: a turn

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-lys291 (accessed [today's date]).

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