Is FANCL p.Ala2= (c.6G>A) pathogenic?

FANCL p.Ala2= (c.6G>A) is classified Likely benign in FANCL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). Very rare (popmax 0.00445%, eas); Associated with Fanconi anemia.

What condition is associated with FANCL p.Ala2= (c.6G>A)?

FANCL p.Ala2= (c.6G>A) is associated with Fanconi anemia (ClinVar).

How common is FANCL p.Ala2= (c.6G>A) in the general population?

FANCL p.Ala2= (c.6G>A) is very rare (popmax 0.00445%, eas) (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.Ala2=

c.6G>A · rs781559042 · VCV1107253

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.024	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -0.15, phastCons 0.006
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,896 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000186% 3/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,448
European (non-Finnish)	8.47e-05%	1,180,038

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.Ala2=
Coding: c.6G>A
MANE Select: NM_018062
dbSNP: rs781559042
Type: single nucleotide variant
Location: chr2:58241308 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.36 · 8 PDB
Residue 2: a modified residue (n-acetylalanine)

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 p.Ala2Ser Uncertain significance ★★ ⚠ same residue
FANCL p.Ala2Val Uncertain significance ★★ ⚠ same residue
FANCL p.Ala2Thr Uncertain significance ★ ⚠ same residue
FANCL p.Ala2Gly Uncertain significance ★ ⚠ same residue
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

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-ala2 (accessed [today's date]).

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