Is FANCC p.Ser5= (c.15A>T) pathogenic?

FANCC p.Ser5= (c.15A>T) is classified Likely benign in FANCC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). Very rare (popmax 0.0011%, sas); Associated with Fanconi anemia.

What condition is associated with FANCC p.Ser5= (c.15A>T)?

FANCC p.Ser5= (c.15A>T) is associated with Fanconi anemia (ClinVar).

How common is FANCC p.Ser5= (c.15A>T) in the general population?

FANCC p.Ser5= (c.15A>T) is very rare (popmax 0.0011%, 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.

FANCC p.Ser5=

c.15A>T · rs778408360 · VCV2856842

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.47	GERP -2.2
Overall
CADD	4.438	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 6.2e-05% 1/1,614,098 alleles · very rare exomes 1/1,461,798 · genomes 0/152,300 · joint denominator

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.Ser5=
Coding: c.15A>T
MANE Select: NM_000136
dbSNP: rs778408360
Type: single nucleotide variant
Location: chr9:95249277 (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

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCC p.Ser5Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FANCC p.Ser5Ter Pathogenic ★ 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-ser5 (accessed [today's date]).

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