Is FANCC p.Pro248= (c.744C>T) pathogenic?

FANCC p.Pro248= (c.744C>T) is classified Likely benign in FANCC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-05). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with FANCC p.Pro248= (c.744C>T)?

FANCC p.Pro248= (c.744C>T) is associated with hereditary neoplastic syndrome, Fanconi anemia (ClinVar).

How common is FANCC p.Pro248= (c.744C>T) in the general population?

FANCC p.Pro248= (c.744C>T) is absent from gnomAD v4.1 (gnomAD).

FANCC p.Pro248=

c.744C>T · rs758201013 · VCV1127041

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

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 2.4	GERP 0.098, phastCons 1
Overall
CADD	8.475	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.Pro248=
Coding: c.744C>T
MANE Select: NM_000136
dbSNP: rs758201013
Type: single nucleotide variant
Location: chr9:95135445 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB
Residue 248: an α-helix

Full FANCC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia

Similar variants

FANCC p.Pro248Ser 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
FANCC c.346-1G>A Pathogenic/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-pro248 (accessed [today's date]).

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