Is FANCD2 p.Pro732= (c.2196G>A) pathogenic?

FANCD2 p.Pro732= (c.2196G>A) is classified Likely benign in FANCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-19). Ultra-rare (popmax 0.0201%, eas); Associated with Fanconi anemia.

What condition is associated with FANCD2 p.Pro732= (c.2196G>A)?

FANCD2 p.Pro732= (c.2196G>A) is associated with Fanconi anemia (ClinVar).

How common is FANCD2 p.Pro732= (c.2196G>A) in the general population?

FANCD2 p.Pro732= (c.2196G>A) is ultra-rare (popmax 0.0201%, 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.

FANCD2 p.Pro732=

c.2196G>A · rs200848801 · VCV1131732

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

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 1.1	GERP -0.46, phastCons 1
Overall
CADD	14.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,882 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00174% 28/1,613,766 alleles · ultra-rare exomes 26/1,461,484 · genomes 2/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
South Asian	0.0022%	45,532
Admixed American	0.00167%	60,012
European (non-Finnish)	0.00136%	73,731

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: FANCD2
Protein: p.Pro732=
Coding: c.2196G>A
MANE Select: NM_001018115
dbSNP: rs200848801
Type: single nucleotide variant
Location: chr3:10065421 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.24 · 13 PDB
Residue 732: an α-helix

Full FANCD2 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

FANCD2 p.Pro732Leu Uncertain significance ★ ⚠ same residue
FANCD2 c.1948-6C>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.206-1G>T Likely pathogenic ★★ same condition
FANCD2 c.2169-1G>C Likely pathogenic ★★ same condition
FANCD2 c.2269+1G>A Likely pathogenic ★★ same condition
FANCD2 c.2715+1G>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.3224+1G>T Likely pathogenic ★★ same condition
FANCD2 c.3467-2A>G 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/fancd2-p-pro732 (accessed [today's date]).

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