Is FANCF p.Phe72Val (c.214T>G) pathogenic?

FANCF p.Phe72Val (c.214T>G) is classified Uncertain significance in FANCF (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-04). AlphaMissense: likely benign (0.0874); Ultra-rare (popmax 0.0307%, sas); Associated with Fanconi anemia.

What condition is associated with FANCF p.Phe72Val (c.214T>G)?

FANCF p.Phe72Val (c.214T>G) is associated with Fanconi anemia (ClinVar).

How common is FANCF p.Phe72Val (c.214T>G) in the general population?

FANCF p.Phe72Val (c.214T>G) is ultra-rare (popmax 0.0307%, sas) (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.Phe72Val (c.214T>G)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

FANCF p.Phe72Val

c.214T>G · rs574667155 · VCV2144978

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
SaProt	LLR -4.67	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.8	GERP -3.4
Regional constraint	o/e 1.15	unconstrained · MANE · 1,121 bp · p 0.0014 · regional, not allelic
Overall
CADD	0.504	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; SaProt is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% South Asian · 28/91,088 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00186% 30/1,613,822 alleles · ultra-rare exomes 29/1,461,508 · genomes 1/152,314 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0307%	3,253
European (non-Finnish)	0.000169%	589,995

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.Phe72Val
Coding: c.214T>G
MANE Select: NM_022725
dbSNP: rs574667155
Type: single nucleotide variant
Location: chr11:22625597 (GRCh38)
Structure: AlphaFold pLDDT 78.87 · 7 PDB

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

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

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-phe72val (accessed [today's date]).

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