Is FANCL p.Pro293= (c.879A>T) pathogenic?

FANCL p.Pro293= (c.879A>T) is classified Likely benign in FANCL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-16). Very rare (popmax 0.00167%, amr); Associated with Fanconi anemia.

What condition is associated with FANCL p.Pro293= (c.879A>T)?

FANCL p.Pro293= (c.879A>T) is associated with Fanconi anemia (ClinVar).

How common is FANCL p.Pro293= (c.879A>T) in the general population?

FANCL p.Pro293= (c.879A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

FANCL p.Pro293=

c.879A>T · rs1217731968 · VCV1580437

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	phastCons 1
Overall
CADD	17.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,916 alleles

Overall 0.000186% 3/1,612,608 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,916
Remaining individualsnot grpmax-eligible	0.0016%	62,410
African / African-American	0.00134%	74,868

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: FANCL
Protein: p.Pro293=
Coding: c.879A>T
MANE Select: NM_018062
dbSNP: rs1217731968
Type: single nucleotide variant
Location: chr2:58162890 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 8 PDB
Residue 293: the 'ubc-rwd region (urd)' region

Full FANCL 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

FANCL c.1021-2A>G Likely pathogenic ★★ same condition
FANCL c.156-2A>T Likely pathogenic ★★ same condition
FANCL c.273+1G>A Likely pathogenic ★★ same condition
FANCL c.471+2T>C Likely pathogenic ★★ same condition
FANCL c.472-1G>C Pathogenic/Likely pathogenic ★★ same condition
FANCL c.903+1G>T Pathogenic/Likely pathogenic ★★ same condition
FANCL p.Arg68Ter Pathogenic/Likely pathogenic ★★ same condition
FANCL p.Gln189Ter 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/fancl-p-pro293 (accessed [today's date]).

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