Is FANCC p.Pro342Ser (c.1024C>T) pathogenic?

FANCC p.Pro342Ser (c.1024C>T) is classified Uncertain significance in FANCC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-16). AlphaMissense: ambiguous (0.3607); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with FANCC p.Pro342Ser (c.1024C>T)?

FANCC p.Pro342Ser (c.1024C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is FANCC p.Pro342Ser (c.1024C>T) in the general population?

FANCC p.Pro342Ser (c.1024C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FANCC p.Pro342Ser (c.1024C>T)?

AlphaMissense predicts ambiguous (score 0.3607) — an in-silico prediction, not a clinical call.

FANCC p.Pro342Ser

c.1024C>T · rs863224606 · VCV2450921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

⚠ 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	0.3607	ambiguous
REVEL	0.592	indeterminate
SaProt	LLR -10.26	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 148 kb · p 0.78 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

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.Pro342Ser
Coding: c.1024C>T
MANE Select: NM_000136
dbSNP: rs863224606
Type: single nucleotide variant
Location: chr9:95117363 (GRCh38)

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

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-pro342ser (accessed [today's date]).

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