Is CARD11 p.Asp604= (c.1812C>T) pathogenic?

CARD11 p.Asp604= (c.1812C>T) is classified Benign/Likely benign in CARD11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-31). Rare (popmax 0.452%, afr); Associated with severe combined immunodeficiency due to CARD11 deficiency.

What condition is associated with CARD11 p.Asp604= (c.1812C>T)?

CARD11 p.Asp604= (c.1812C>T) is associated with severe combined immunodeficiency due to CARD11 deficiency, BENTA disease (ClinVar).

How common is CARD11 p.Asp604= (c.1812C>T) in the general population?

CARD11 p.Asp604= (c.1812C>T) is rare (popmax 0.452%, afr) (gnomAD).

CARD11 p.Asp604=

Q: How is Combined immunodeficiency due to CARD11 deficiency inherited?

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

c.1812C>T · rs149270244 · VCV772885

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.452%, afr)

Conditions

severe combined immunodeficiency due to CARD11 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 3.3	GERP -0.19, phastCons 1
Overall
CADD	9.849	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.452% African / African-American · 339/75,028 alleles

Filtering AF 0.412% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.397%

Overall 0.0248% 400/1,613,632 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.452%	221
Remaining individualsnot grpmax-eligible	0.0544%	1,838
Admixed American	0.035%	2,857
Middle Eastern	0.0166%	6,010
South Asian	0.0011%	91,046
European (non-Finnish)	0.000339%	294,984

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: CARD11
Protein: p.Asp604=
Coding: c.1812C>T
MANE Select: NM_032415
dbSNP: rs149270244
Type: single nucleotide variant
Location: chr7:2924361 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 604: the 'inhibitory domain (id)' region; the 'disordered' region

Full CARD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

severe combined immunodeficiency due to CARD11 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BENTA disease

For Combined immunodeficiency due to CARD11 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CARD11 p.Asp604Asn Uncertain significance ★ ⚠ same residue
CARD11 p.Arg30Trp Pathogenic/Likely pathogenic ★★ same condition
CARD11 p.Arg47His Pathogenic/Likely pathogenic ★★ same condition
CARD11 p.Arg837Ter Pathogenic ★★ same condition
CARD11 p.Gly123Asp Pathogenic ★★ ⚠ same condition
CARD11 p.Gly123Ser Pathogenic ★★ ⚠ same condition
CARD11 c.1807+5G>A Uncertain significance ★★ same condition
CARD11 c.2269+3G>A 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/card11-p-asp604 (accessed [today's date]).

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