Is FANCC p.Phe341= (c.1023T>C) pathogenic?

FANCC p.Phe341= (c.1023T>C) is classified Likely benign in FANCC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-01). Very rare (popmax 0.005%, amr); Associated with Fanconi anemia.

What condition is associated with FANCC p.Phe341= (c.1023T>C)?

FANCC p.Phe341= (c.1023T>C) is associated with Fanconi anemia, Fanconi anemia complementation group C, hereditary neoplastic syndrome (ClinVar).

How common is FANCC p.Phe341= (c.1023T>C) in the general population?

FANCC p.Phe341= (c.1023T>C) is very rare (popmax 0.005%, amr) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FANCC p.Phe341=

c.1023T>C · rs758439579 · VCV526470

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.079	GERP -2.2, phastCons 0.052
Overall
CADD	6.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,010 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,614,118 alleles · very rare exomes 4/1,461,810 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	8.47e-05%	1,180,034

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: FANCC
Protein: p.Phe341=
Coding: c.1023T>C
MANE Select: NM_000136
dbSNP: rs758439579
Type: single nucleotide variant
Location: chr9:95117364 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB

Full FANCC 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 C hereditary neoplastic syndrome

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCC p.Phe341Cys Uncertain significance ★★ ⚠ same residue
FANCC p.Phe341Leu Uncertain significance ★★ ⚠ same residue
FANCC c.1073-1G>C Pathogenic/Likely pathogenic ★★ same condition
FANCC c.1155-1G>C Pathogenic/Likely pathogenic ★★ same condition
FANCC c.165+1G>T Pathogenic/Likely pathogenic ★★ same condition
FANCC c.166-2A>G Pathogenic/Likely pathogenic ★★ same condition
FANCC c.251-2A>C Pathogenic/Likely pathogenic ★★ same condition
FANCC c.345+1G>A Likely pathogenic ★★ 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/fancc-p-phe341 (accessed [today's date]).

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