Is FANCF p.Tyr287Cys (c.860A>G) pathogenic?

FANCF p.Tyr287Cys (c.860A>G) is classified Uncertain significance in FANCF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.6325); Ultra-rare (popmax 0.0235%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCF p.Tyr287Cys (c.860A>G)?

FANCF p.Tyr287Cys (c.860A>G) is associated with Fanconi anemia, Fanconi anemia complementation group F (ClinVar).

How common is FANCF p.Tyr287Cys (c.860A>G) in the general population?

FANCF p.Tyr287Cys (c.860A>G) is ultra-rare (popmax 0.0235%, nfe) (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 FANCF p.Tyr287Cys (c.860A>G)?

AlphaMissense predicts likely pathogenic (score 0.6325) — an in-silico prediction, not a clinical call.

FANCF p.Tyr287Cys

c.860A>G · rs750623273 · VCV304201

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6325 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0235%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.6325	likely pathogenic
REVEL	0.195	benign-leaning
SaProt	LLR -10.25	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0235% European (non-Finnish) · 277/1,180,042 alleles

Filtering AF 0.0212% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0203%

Overall 0.018% 290/1,614,060 alleles · ultra-rare exomes 277/1,461,892 · genomes 13/152,168 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0235%	4,260
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.00267%	37,461
South Asian	0.0011%	91,082

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.Tyr287Cys
Coding: c.860A>G
MANE Select: NM_022725
dbSNP: rs750623273
Type: single nucleotide variant
Location: chr11:22624951 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 287: a β-strand

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.Tyr287= Likely benign ★ 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 c.-21A>G Uncertain significance ★★ same condition
FANCF c.-31T>C Uncertain significance ★★ same condition
FANCF c.*1879T>C 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-tyr287cys (accessed [today's date]).

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