Is CARD11 p.Asp1007Glu (c.3021T>G) pathogenic?

CARD11 p.Asp1007Glu (c.3021T>G) is classified Uncertain significance in CARD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-03-14). AlphaMissense: ambiguous (0.371); Ultra-rare (popmax 0.012%, afr); Associated with severe combined immunodeficiency due to CARD11 deficiency.

What condition is associated with CARD11 p.Asp1007Glu (c.3021T>G)?

CARD11 p.Asp1007Glu (c.3021T>G) is associated with severe combined immunodeficiency due to CARD11 deficiency, BENTA disease (ClinVar).

How common is CARD11 p.Asp1007Glu (c.3021T>G) in the general population?

CARD11 p.Asp1007Glu (c.3021T>G) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about CARD11 p.Asp1007Glu (c.3021T>G)?

AlphaMissense predicts ambiguous (score 0.371) — an in-silico prediction, not a clinical call.

CARD11 p.Asp1007Glu

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.3021T>G · rs780981181 · VCV2394813

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.371 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

severe combined immunodeficiency due to CARD11 deficiency

Computational evidence

Protein change
AlphaMissense	0.371	ambiguous
REVEL	0.118	moderately benign-leaning
SaProt	LLR -5.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -2.4
Regional constraint	o/e 0.86	unconstrained · MANE · 31 kb · p 2.9e-06 · regional, not allelic
Overall
CADD	12.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,890 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00062% 10/1,613,490 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,321
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Asp1007Glu
Coding: c.3021T>G
MANE Select: NM_032415
dbSNP: rs780981181
Type: single nucleotide variant
Location: chr7:2912295 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 1007: the guanylate kinase-like domain; a UniProt-annotated variant site (in imd11a; results in defective nf-kappa-b activation)

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.Asp1007Gly 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-asp1007glu (accessed [today's date]).

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