Is FANCF p.Arg284Pro (c.851G>C) pathogenic?

FANCF p.Arg284Pro (c.851G>C) is classified Uncertain significance in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-10). AlphaMissense: likely pathogenic (0.5641); Very rare (popmax 0.00223%, eas); Associated with Fanconi anemia.

What condition is associated with FANCF p.Arg284Pro (c.851G>C)?

FANCF p.Arg284Pro (c.851G>C) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Arg284Pro (c.851G>C) in the general population?

FANCF p.Arg284Pro (c.851G>C) is very rare (popmax 0.00223%, eas) (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.Arg284Pro (c.851G>C)?

AlphaMissense predicts likely pathogenic (score 0.5641) — an in-silico prediction, not a clinical call.

FANCF p.Arg284Pro

c.851G>C · rs768798175 · VCV1980767

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.5641	likely pathogenic
REVEL	0.243	benign-leaning
SaProt	LLR -12.25	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 -5	GERP -3.4
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	4.858	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 0.00223% East Asian · 1/44,882 alleles

Overall 0.000186% 3/1,614,204 alleles · very rare exomes 3/1,461,892 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
African / African-American	0.00133%	75,040
European (non-Finnish)	8.47e-05%	1,180,044

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.Arg284Pro
Coding: c.851G>C
MANE Select: NM_022725
dbSNP: rs768798175
Type: single nucleotide variant
Location: chr11:22624960 (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

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-arg284pro (accessed [today's date]).

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