Is FANCC p.Pro541= (c.1623T>G) pathogenic?

FANCC p.Pro541= (c.1623T>G) is classified Likely benign in FANCC (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-13). Ultra-rare (popmax 0.016%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with FANCC p.Pro541= (c.1623T>G)?

FANCC p.Pro541= (c.1623T>G) is associated with hereditary neoplastic syndrome, Fanconi anemia (ClinVar).

How common is FANCC p.Pro541= (c.1623T>G) in the general population?

FANCC p.Pro541= (c.1623T>G) is ultra-rare (popmax 0.016%, afr) (gnomAD).

FANCC p.Pro541=

c.1623T>G · rs375362894 · VCV215637

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -7.2	GERP -3.1
Overall
CADD	0.139	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/75,056 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.000867% 14/1,614,146 alleles · ultra-rare exomes 7/1,461,832 · genomes 7/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,255
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,510

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FANCC
Protein: p.Pro541=
Coding: c.1623T>G
MANE Select: NM_000136
dbSNP: rs375362894
Type: single nucleotide variant
Location: chr9:95101761 (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

Also linked: Fanconi anemia

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-pro541 (accessed [today's date]).

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