Is FANCF p.Pro213Ser (c.637C>T) pathogenic?

FANCF p.Pro213Ser (c.637C>T) is classified Conflicting classifications of pathogenicity in FANCF (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0767); Rare (popmax 0.133%, amr); Associated with Inborn genetic diseases.

What condition is associated with FANCF p.Pro213Ser (c.637C>T)?

FANCF p.Pro213Ser (c.637C>T) is associated with Inborn genetic diseases, Fanconi anemia complementation group F, Fanconi anemia (ClinVar).

How common is FANCF p.Pro213Ser (c.637C>T) in the general population?

FANCF p.Pro213Ser (c.637C>T) is rare (popmax 0.133%, amr) (gnomAD).

What do computational predictors say about FANCF p.Pro213Ser (c.637C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

FANCF p.Pro213Ser

c.637C>T · rs201382399 · VCV659459

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.76	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 0.57	GERP -0.085, phastCons 0.001
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	5.426	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 0.133% Admixed American · 79/59,440 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00603% 97/1,609,696 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.133%	752
Remaining individualsnot grpmax-eligible	0.0273%	3,661
European (non-Finnish)	8.49e-05%	1,177,504

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.Pro213Ser
Coding: c.637C>T
MANE Select: NM_022725
dbSNP: rs201382399
Type: single nucleotide variant
Location: chr11:22625174 (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

Also linked: Fanconi anemia complementation group F 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 c.-21A>G Uncertain significance ★★ same condition
FANCF c.-31T>C Uncertain significance ★★ same condition
FANCF c.*1879T>C Uncertain significance ★★ same condition
FANCF p.Ala124Ser 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-pro213ser (accessed [today's date]).

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