Is CARD9 p.Arg364= (c.1090C>A) pathogenic?

CARD9 p.Arg364= (c.1090C>A) is classified Conflicting classifications of pathogenicity in CARD9 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-28). Rare (popmax 0.348%, eas); Associated with predisposition to invasive fungal disease due to CARD9 deficiency.

What condition is associated with CARD9 p.Arg364= (c.1090C>A)?

CARD9 p.Arg364= (c.1090C>A) is associated with predisposition to invasive fungal disease due to CARD9 deficiency (ClinVar).

How common is CARD9 p.Arg364= (c.1090C>A) in the general population?

CARD9 p.Arg364= (c.1090C>A) is rare (popmax 0.348%, eas) (gnomAD).

CARD9 p.Arg364=

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.1090C>A · rs151211588 · VCV365840

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.348%, eas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP -0.94, phastCons 0.14
Overall
CADD	3.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.348% East Asian · 156/44,792 alleles

Filtering AF 0.304% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.287%

Overall 0.0102% 163/1,600,364 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.348%	287
Remaining individualsnot grpmax-eligible	0.00803%	12,456
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,498
European (non-Finnish)	8.49e-05%	1,178,478

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: CARD9
Protein: p.Arg364=
Coding: c.1090C>A
MANE Select: NM_052813
dbSNP: rs151211588
Type: single nucleotide variant
Location: chr9:136367816 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.24 · 8 PDB
Residue 364: 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.Arg364Trp Uncertain significance ★★ ⚠ same residue
CARD9 p.Arg364Gln Uncertain significance ★ ⚠ same residue
CARD9 p.Arg364Leu Uncertain significance ★ ⚠ same residue
CARD9 p.Gln289Ter Pathogenic ★★ same condition
CARD9 p.Gln295Ter Pathogenic ★★ same condition
CARD9 c.-126C>A Uncertain significance ★★ same condition
CARD9 p.Ala109Val Uncertain significance ★★ ⚠ same condition
CARD9 p.Ala190Val Uncertain significance ★★ ⚠ 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-arg364 (accessed [today's date]).

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