Is FANCF p.Leu4Phe (c.10C>T) pathogenic?

FANCF p.Leu4Phe (c.10C>T) is classified Uncertain significance in FANCF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-01). AlphaMissense: likely benign (0.2642); Very rare (popmax 0.00186%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FANCF p.Leu4Phe (c.10C>T)?

FANCF p.Leu4Phe (c.10C>T) is associated with Inborn genetic diseases, Fanconi anemia (ClinVar).

How common is FANCF p.Leu4Phe (c.10C>T) in the general population?

FANCF p.Leu4Phe (c.10C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about FANCF p.Leu4Phe (c.10C>T)?

AlphaMissense predicts likely benign (score 0.2642) — an in-silico prediction, not a clinical call.

FANCF p.Leu4Phe

c.10C>T · rs780551069 · VCV2147930

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2642	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -6.93	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 4.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	23.3	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 0.00186% European (non-Finnish) · 22/1,180,040 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00142% 23/1,614,102 alleles · very rare exomes 23/1,461,782 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,638
African / African-American	0.00133%	75,048

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.Leu4Phe
Coding: c.10C>T
MANE Select: NM_022725
dbSNP: rs780551069
Type: single nucleotide variant
Location: chr11:22625801 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 4: an α-helix

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

Also linked: Fanconi anemia

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-leu4phe (accessed [today's date]).

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