Is FANCC p.Phe44Ser (c.131T>C) pathogenic?

FANCC p.Phe44Ser (c.131T>C) is classified Uncertain significance in FANCC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). AlphaMissense: likely pathogenic (0.8291); Absent from gnomAD v4.1; Associated with Fanconi anemia.

What condition is associated with FANCC p.Phe44Ser (c.131T>C)?

FANCC p.Phe44Ser (c.131T>C) is associated with Fanconi anemia (ClinVar).

How common is FANCC p.Phe44Ser (c.131T>C) in the general population?

FANCC p.Phe44Ser (c.131T>C) 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.Phe44Ser (c.131T>C)?

AlphaMissense predicts likely pathogenic (score 0.8291) — an in-silico prediction, not a clinical call.

FANCC p.Phe44Ser

c.131T>C · rs1588353402 · VCV656772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8291 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.8291	likely pathogenic · top 2% in FANCC
REVEL	0.802	moderately pathogenic-leaning
SaProt	LLR -11.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 148 kb · p 0.78 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Phe44Ser
Coding: c.131T>C
MANE Select: NM_000136
dbSNP: rs1588353402
Type: single nucleotide variant
Location: chr9:95249161 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB
Residue 44: an α-helix

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.Phe44= Benign/Likely benign ★★ same residue
FANCC p.Phe44Cys Uncertain significance ★ ⚠ same residue
FANCC p.Phe44Leu 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

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-phe44ser (accessed [today's date]).

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