Is FANCC p.Pro142Ala (c.424C>G) pathogenic?

FANCC p.Pro142Ala (c.424C>G) is classified Uncertain significance in FANCC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-10-12). AlphaMissense: likely benign (0.0907); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with FANCC p.Pro142Ala (c.424C>G)?

FANCC p.Pro142Ala (c.424C>G) is associated with hereditary neoplastic syndrome, Fanconi anemia (ClinVar).

How common is FANCC p.Pro142Ala (c.424C>G) in the general population?

FANCC p.Pro142Ala (c.424C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FANCC p.Pro142Ala (c.424C>G)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

FANCC p.Pro142Ala

c.424C>G · rs864622581 · VCV220563

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.217	benign-leaning
SaProt	LLR -5.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 1.3, phastCons 0.4
Regional constraint	o/e 1.01	unconstrained · MANE · 148 kb · p 0.78 · regional, not allelic
Overall
CADD	16.25	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.Pro142Ala
Coding: c.424C>G
MANE Select: NM_000136
dbSNP: rs864622581
Type: single nucleotide variant
Location: chr9:95172069 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.39 · 6 PDB
Residue 142: 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.Pro142His Uncertain significance ★★ ⚠ same residue
FANCC p.Pro142Leu 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

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-pro142ala (accessed [today's date]).

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