Is FANCF p.Val23Phe (c.67G>T) pathogenic?

FANCF p.Val23Phe (c.67G>T) is classified Uncertain significance in FANCF (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-08-06). AlphaMissense: likely pathogenic (0.8604); Very rare (popmax 0.00873%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FANCF p.Val23Phe (c.67G>T)?

FANCF p.Val23Phe (c.67G>T) is associated with Inborn genetic diseases, Fanconi anemia complementation group F, Fanconi anemia (ClinVar).

How common is FANCF p.Val23Phe (c.67G>T) in the general population?

FANCF p.Val23Phe (c.67G>T) is very rare (popmax 0.00873%, nfe) (gnomAD).

What do computational predictors say about FANCF p.Val23Phe (c.67G>T)?

AlphaMissense predicts likely pathogenic (score 0.8604) — an in-silico prediction, not a clinical call.

FANCF p.Val23Phe

c.67G>T · rs777143902 · VCV408147

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.8604 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8604	likely pathogenic · top 5% in FANCF
REVEL	0.251	benign-leaning
SaProt	LLR -13.56	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 5.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	26.2	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 0.00873% European (non-Finnish) · 103/1,180,040 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00684%

Overall 0.00669% 108/1,614,040 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00873%	11,457
Remaining individualsnot grpmax-eligible	0.0048%	20,829
African / African-American	0.00267%	37,475

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.Val23Phe
Coding: c.67G>T
MANE Select: NM_022725
dbSNP: rs777143902
Type: single nucleotide variant
Location: chr11:22625744 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB
Residue 23: a turn

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 complementation group F Fanconi anemia

Similar variants

FANCF p.Val23Ile Uncertain significance ★★ ⚠ same residue
FANCF p.Val23= Likely benign ★ 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-val23phe (accessed [today's date]).

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