Is CARD9 p.Lys129= (c.387G>A) pathogenic?

CARD9 p.Lys129= (c.387G>A) is classified Likely benign in CARD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-27). Very rare (popmax 0.0033%, sas); Associated with predisposition to invasive fungal disease due to CARD9 deficiency.

What condition is associated with CARD9 p.Lys129= (c.387G>A)?

CARD9 p.Lys129= (c.387G>A) is associated with predisposition to invasive fungal disease due to CARD9 deficiency (ClinVar).

How common is CARD9 p.Lys129= (c.387G>A) in the general population?

CARD9 p.Lys129= (c.387G>A) is very rare (popmax 0.0033%, sas) (gnomAD).

CARD9 p.Lys129=

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.387G>A · VCV3680747

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

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 -0.039	GERP -2.6, phastCons 0.67
Overall
CADD	7.291	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/91,024 alleles

Filtering AF 0.000876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000274% 4/1,460,382 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,341
European (non-Finnish)	8.47e-05%	1,179,952

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.Lys129=
Coding: c.387G>A
MANE Select: NM_052813
Type: single nucleotide variant
Location: chr9:136371081 (GRCh38)
Gene constraint: LOEUF 1.143 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.24 · 8 PDB
Residue 129: a UniProt-annotated variant site (in imd103; reduced cytokine production in response to c.albicans infection; impaired nf-kappa-b transcriptional activity); an α-helix

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.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-lys129 (accessed [today's date]).

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