Is CARD9 p.Leu482= (c.1446G>C) pathogenic?

CARD9 p.Leu482= (c.1446G>C) is classified Likely benign in CARD9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-31). Very rare (popmax 0.00119%, sas); Associated with Inborn genetic diseases.

What condition is associated with CARD9 p.Leu482= (c.1446G>C)?

CARD9 p.Leu482= (c.1446G>C) is associated with Inborn genetic diseases, predisposition to invasive fungal disease due to CARD9 deficiency (ClinVar).

How common is CARD9 p.Leu482= (c.1446G>C) in the general population?

CARD9 p.Leu482= (c.1446G>C) is very rare (popmax 0.00119%, sas) (gnomAD).

CARD9 p.Leu482=

c.1446G>C · rs1833070000 · VCV1556344

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Conditions

Inborn genetic diseases

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 1.2	GERP -1.4, phastCons 0.001
Overall
CADD	8.465	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00119% South Asian · 1/83,968 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000216% 3/1,386,442 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	83,968
European (non-Finnish)	0.000174%	573,385

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.Leu482=
Coding: c.1446G>C
MANE Select: NM_052813
dbSNP: rs1833070000
Type: single nucleotide variant
Location: chr9:136364548 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.24 · 8 PDB
Residue 482: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: predisposition to invasive fungal disease due to CARD9 deficiency

Similar variants

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
CARD9 p.Ala198Thr Uncertain significance ★★ ⚠ same condition
CARD9 p.Ala199Val Uncertain significance ★★ ⚠ same condition
CARD9 p.Ala290Val 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-leu482 (accessed [today's date]).

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