Is FANCC p.Pro360Arg (c.1079C>G) pathogenic?

FANCC p.Pro360Arg (c.1079C>G) is classified Uncertain significance in FANCC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-07-26). AlphaMissense: likely benign (0.1357); Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCC p.Pro360Arg (c.1079C>G)?

FANCC p.Pro360Arg (c.1079C>G) is associated with Fanconi anemia, hereditary neoplastic syndrome (ClinVar).

How common is FANCC p.Pro360Arg (c.1079C>G) in the general population?

FANCC p.Pro360Arg (c.1079C>G) 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.

What do computational predictors say about FANCC p.Pro360Arg (c.1079C>G)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

FANCC p.Pro360Arg

c.1079C>G · rs730881721 · VCV655190

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Fanconi anemia

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -9.05	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 148 kb · p 0.78 · regional, not allelic
Overall
CADD	20.2	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; REVEL and SaProt are independent agreement signals.

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.Pro360Arg
Coding: c.1079C>G
MANE Select: NM_000136
dbSNP: rs730881721
Type: single nucleotide variant
Location: chr9:95114704 (GRCh38)

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

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-pro360arg (accessed [today's date]).

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