Is FANCF p.Val77fs (c.230_252del) pathogenic?

FANCF p.Val77fs (c.230252del) is classified Pathogenic in FANCF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-06-19). Very rare (popmax 0.00934%, afr); Associated with Fanconi anemia.

What condition is associated with FANCF p.Val77fs (c.230_252del)?

FANCF p.Val77fs (c.230_252del) is associated with Fanconi anemia, Fanconi anemia complementation group F (ClinVar).

How common is FANCF p.Val77fs (c.230_252del) in the general population?

FANCF p.Val77fs (c.230_252del) is very rare (popmax 0.00934%, afr) (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.Val77fs

c.230_252del · rs730880277 · VCV6340

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

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 2.1	GERP -1.8, phastCons 0.81
Overall
CADD	29.6	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

Grpmax group 0.00934% African / African-American · 7/74,944 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000558% 9/1,613,946 alleles · very rare exomes 7/1,461,714 · genomes 2/152,232 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,706
Admixed American	0.00333%	30,005

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.Val77fs
Coding: c.230_252del
MANE Select: NM_022725
dbSNP: rs730880277
Type: Deletion
Location: chr11:22625559 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB

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

Also linked: Fanconi anemia complementation group F

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCF p.Val77= Likely benign ★ same residue
FANCF p.Ala180fs Pathogenic ★★ same condition
FANCF p.Ala29fs Pathogenic ★★ same condition
FANCF p.Arg74fs Pathogenic ★★ same condition
FANCF p.Gly231fs Likely pathogenic ★★ same condition
FANCF p.Gly233fs Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Phe201_Leu202insTer Pathogenic/Likely pathogenic ★★ same condition
FANCF p.Val177fs 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/fancf-p-val77fs (accessed [today's date]).

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