Is FANCF p.Pro320Leu (c.959C>T) pathogenic?

FANCF p.Pro320Leu (c.959C>T) is classified Benign/Likely benign in FANCF (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1298); Low-frequency (popmax 1.8%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCF p.Pro320Leu (c.959C>T)?

FANCF p.Pro320Leu (c.959C>T) is associated with Fanconi anemia, Fanconi anemia complementation group F (ClinVar).

How common is FANCF p.Pro320Leu (c.959C>T) in the general population?

FANCF p.Pro320Leu (c.959C>T) is low-frequency (popmax 1.8%, 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.Pro320Leu (c.959C>T)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

FANCF p.Pro320Leu

c.959C>T · rs45451294 · VCV134351

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.8%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -7.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.4	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	18.42	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 1.8% European (non-Finnish) · 21,258/1,179,998 alleles

Filtering AF 1.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.77%

Overall 1.57% 25,351/1,614,116 alleles · low-frequency exomes 23,613/1,461,874 · genomes 1,738/152,242 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	2.74%	37
European (non-Finnish)grpmax	1.8%	56
Remaining individualsnot grpmax-eligible	1.58%	63
Middle Eastern	1.42%	70
Admixed American	1.11%	90
South Asian	1.09%	91
Amishnot grpmax-eligible	0.658%	152
Finnishnot grpmax-eligible	0.462%	216
African / African-American	0.321%	311
East Asian	0.00891%	11,218

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro320Leu
Coding: c.959C>T
MANE Select: NM_022725
dbSNP: rs45451294
Type: single nucleotide variant
Location: chr11:22624852 (GRCh38)

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

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-pro320leu (accessed [today's date]).

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