Is FANCF p.Phe83= (c.249C>T) pathogenic?

FANCF p.Phe83= (c.249C>T) is classified Likely benign in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-19). Ultra-rare (popmax 0.0165%, mid); Associated with Fanconi anemia.

What condition is associated with FANCF p.Phe83= (c.249C>T)?

FANCF p.Phe83= (c.249C>T) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Phe83= (c.249C>T) in the general population?

FANCF p.Phe83= (c.249C>T) is ultra-rare (popmax 0.0165%, 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.Phe83=

c.249C>T · rs1858633603 · VCV1118741

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.038	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1, phastCons 1
Overall
CADD	6.627	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000274% 4/1,461,730 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	8.47e-05%	1,180,020

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.Phe83=
Coding: c.249C>T
MANE Select: NM_022725
dbSNP: rs1858633603
Type: single nucleotide variant
Location: chr11:22625562 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 83: 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.Phe83Ser 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-phe83 (accessed [today's date]).

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