Is FANCD2 p.Ser64fs (c.192_195del) pathogenic?

FANCD2 p.Ser64fs (c.192195del) is classified Pathogenic/Likely pathogenic in FANCD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-28). Very rare (popmax 0.00165%, nfe); Associated with Fanconi anemia.

What condition is associated with FANCD2 p.Ser64fs (c.192_195del)?

FANCD2 p.Ser64fs (c.192_195del) is associated with Fanconi anemia, Fanconi anemia complementation group D2 (ClinVar).

How common is FANCD2 p.Ser64fs (c.192_195del) in the general population?

FANCD2 p.Ser64fs (c.192_195del) is very rare (popmax 0.00165%, 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.

FANCD2 p.Ser64fs

c.192_195del · rs1221526082 · VCV961904

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00165%, nfe)

Conditions

Fanconi anemia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP -0.12, phastCons 0.077

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00165% European (non-Finnish) · 19/1,153,476 alleles

Filtering AF 0.00105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000849%

Overall 0.0012% 19/1,584,662 alleles · very rare exomes 19/1,432,364 · genomes 0/152,298 · 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.Ser64fs
Coding: c.192_195del
MANE Select: NM_001018115
dbSNP: rs1221526082
Type: Deletion
Location: chr3:10032957 (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 64: the 'interaction with fance' region; a β-strand

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 c.2609_2613del Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Asn1032fs Likely pathogenic ★★ same condition
FANCD2 p.Gln1100fs Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Glu888fs Pathogenic ★★ same condition
FANCD2 p.Gly1101fs Likely pathogenic ★★ same condition
FANCD2 p.His654fs Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Ile945_Leu946insTer Pathogenic/Likely pathogenic ★★ same condition
FANCD2 p.Leu1364fs Pathogenic/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-ser64fs (accessed [today's date]).

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