Is CARD9 p.Asp451fs (c.1350dup) pathogenic?

CARD9 p.Asp451fs (c.1350dup) is classified Pathogenic in CARD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-12). Absent from gnomAD; Associated with predisposition to invasive fungal disease due to CARD9 deficiency.

What condition is associated with CARD9 p.Asp451fs (c.1350dup)?

CARD9 p.Asp451fs (c.1350dup) is associated with predisposition to invasive fungal disease due to CARD9 deficiency (ClinVar).

How common is CARD9 p.Asp451fs (c.1350dup) in the general population?

CARD9 p.Asp451fs (c.1350dup) is absent from gnomAD (gnomAD).

CARD9 p.Asp451fs

Q: How is Predisposition to invasive fungal disease due to CARD9 deficiency inherited?

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

c.1350dup · rs1260364391 · VCV2040735

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

predisposition to invasive fungal disease due to CARD9 deficiency

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 10 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 0.83

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CARD9
Protein: p.Asp451fs
Coding: c.1350dup
MANE Select: NM_052813
dbSNP: rs1260364391
Type: Duplication
Location: chr9:136366806 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.24 · 8 PDB
Residue 451: the 'disordered' region; a UniProt-annotated variant site (in imd103; reduced cytokine production in response to c.albicans infection; impaired nf-kappa-b transcriptional activity); a UniProt-annotated variant site (in imd103; decreased production of cytokines in cd4(+) th17 cells); a UniProt-annotated variant site (in imd103; reduced production igg antibodies in response to c.albicans infection); a UniProt-annotated variant site (in imd103; reduced cytokine production in response to c.albicans infection)

Full CARD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

predisposition to invasive fungal disease due to CARD9 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Predisposition to invasive fungal disease due to CARD9 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

CARD9 p.Asp451Asn Uncertain significance ★★ ⚠ same residue
CARD9 p.Asp451= Likely benign ★ same residue
CARD9 p.Asp274fs Pathogenic/Likely pathogenic ★★ same condition
CARD9 c.184+15dup Likely benign ★★ same condition
CARD9 p.Glu194Ter Pathogenic ★ same condition
CARD9 p.Ser431fs Pathogenic ★ same condition
CARD9 c.1270-35_1270-5dup Uncertain significance ★ same condition
CARD9 c.1358-5dup Likely benign ★ 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/card9-p-asp451fs (accessed [today's date]).

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