Is FANCF p.Arg101Trp (c.301C>T) pathogenic?

FANCF p.Arg101Trp (c.301C>T) is classified Uncertain significance in FANCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-11). AlphaMissense: likely benign (0.203); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FANCF p.Arg101Trp (c.301C>T)?

FANCF p.Arg101Trp (c.301C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FANCF p.Arg101Trp (c.301C>T) in the general population?

FANCF p.Arg101Trp (c.301C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about FANCF p.Arg101Trp (c.301C>T)?

AlphaMissense predicts likely benign (score 0.203) — an in-silico prediction, not a clinical call.

FANCF p.Arg101Trp

c.301C>T · rs760571335 · VCV1338057

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.203 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.203	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -10.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.95, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	26.4	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 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,844 alleles · very rare

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.Arg101Trp
Coding: c.301C>T
MANE Select: NM_022725
dbSNP: rs760571335
Type: single nucleotide variant
Location: chr11:22625510 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB

Full FANCF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FANCF p.Arg101Pro Uncertain significance ★★ ⚠ same residue
FANCF p.Arg101Gly Uncertain significance ★★ ⚠ same residue
FANCF p.Arg32His Uncertain significance ★★ ⚠ same condition
FANCF p.Asn82Asp Uncertain significance ★★ ⚠ same condition
FANCF p.Gln130Arg Uncertain significance ★★ ⚠ same condition
FANCF p.Gln219Arg Uncertain significance ★★ ⚠ same condition
FANCF p.Gly75Cys Uncertain significance ★★ ⚠ same condition
FANCF p.Ile205Thr 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-arg101trp (accessed [today's date]).

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