Is FANCF p.Arg50Pro (c.149G>C) pathogenic?

FANCF p.Arg50Pro (c.149G>C) is classified Uncertain significance in FANCF (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-12-14). AlphaMissense: likely benign (0.1828); Very rare (popmax 0.00703%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCF p.Arg50Pro (c.149G>C)?

FANCF p.Arg50Pro (c.149G>C) is associated with Fanconi anemia, Fanconi anemia complementation group F (ClinVar).

How common is FANCF p.Arg50Pro (c.149G>C) in the general population?

FANCF p.Arg50Pro (c.149G>C) is very rare (popmax 0.00703%, 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.Arg50Pro (c.149G>C)?

AlphaMissense predicts likely benign (score 0.1828) — an in-silico prediction, not a clinical call.

FANCF p.Arg50Pro

c.149G>C · rs371420932 · VCV576019

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1828 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00703%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.1828	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -4.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP 0.15
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	17.04	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00703% European (non-Finnish) · 83/1,179,976 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00533%

Overall 0.0052% 84/1,613,844 alleles · very rare exomes 80/1,461,644 · genomes 4/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00703%	14,217
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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.Arg50Pro
Coding: c.149G>C
MANE Select: NM_022725
dbSNP: rs371420932
Type: single nucleotide variant
Location: chr11:22625662 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 50: 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.Arg50Gly Uncertain significance ★ ⚠ same residue
FANCF p.Arg50Trp Conflicting classifications of pathogenicity ★ ⚠ 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

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-arg50pro (accessed [today's date]).

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