Is FANCD2 p.Ala799Asp (c.2396C>A) pathogenic?

FANCD2 p.Ala799Asp (c.2396C>A) is classified Uncertain significance in FANCD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-05). AlphaMissense: likely pathogenic (0.9345); Very rare (popmax 0.000425%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCD2 p.Ala799Asp (c.2396C>A)?

FANCD2 p.Ala799Asp (c.2396C>A) is associated with Fanconi anemia, Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Ala799Asp (c.2396C>A) in the general population?

FANCD2 p.Ala799Asp (c.2396C>A) is very rare (popmax 0.000425%, nfe) (gnomAD).

How is Hereditary isolated aplastic anemia inherited?

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

What do computational predictors say about FANCD2 p.Ala799Asp (c.2396C>A)?

AlphaMissense predicts likely pathogenic (score 0.9345) — an in-silico prediction, not a clinical call.

FANCD2 p.Ala799Asp

c.2396C>A · rs1193547837 · VCV1523758

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9345 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Fanconi anemia

Computational evidence

Protein change
AlphaMissense	0.9345	likely pathogenic · top 4% in FANCD2
REVEL	0.477	indeterminate
SaProt	LLR -8.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 36 kb · p 0.0049 · regional, not allelic
Overall
CADD	24.4	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

Grpmax group 0.000425% European (non-Finnish) · 5/1,175,234 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000311% 5/1,608,662 alleles · very rare exomes 5/1,456,398 · genomes 0/152,264 · joint denominator

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.Ala799Asp
Coding: c.2396C>A
MANE Select: NM_001018115
dbSNP: rs1193547837
Type: single nucleotide variant
Location: chr3:10067219 (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 799: 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

Also linked: Fanconi anemia complementation group D2

For Hereditary isolated aplastic anemia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

Similar variants

FANCD2 p.Ala799= Likely benign ★ same residue
FANCD2 c.1279-1G>A Pathogenic/Likely pathogenic ★★ same condition
FANCD2 c.1279-2A>G Likely pathogenic ★★ same condition
FANCD2 c.1948-16T>G Pathogenic ★★ same condition
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

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-ala799asp (accessed [today's date]).

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