Is FANCC p.Ser280= (c.840G>T) pathogenic?

FANCC p.Ser280= (c.840G>T) is classified Likely benign in FANCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-19). Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCC p.Ser280= (c.840G>T)?

FANCC p.Ser280= (c.840G>T) is associated with Fanconi anemia, hereditary neoplastic syndrome (ClinVar).

How common is FANCC p.Ser280= (c.840G>T) in the general population?

FANCC p.Ser280= (c.840G>T) is absent from gnomAD v4.1 (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.Ser280=

c.840G>T · rs34671520 · VCV1132735

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.8	GERP -4
Overall
CADD	6.956	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FANCC
Protein: p.Ser280=
Coding: c.840G>T
MANE Select: NM_000136
dbSNP: rs34671520
Type: single nucleotide variant
Location: chr9:95135349 (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: hereditary neoplastic syndrome

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

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
FANCC c.346-1G>A Pathogenic/Likely pathogenic ★★ same condition
FANCC c.456+4A>T 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-ser280 (accessed [today's date]).

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