Is CARD11 p.Asp629= (c.1887T>C) pathogenic?

CARD11 p.Asp629= (c.1887T>C) is classified Likely benign in CARD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-15). Very rare (popmax 0.00449%, nfe); Associated with severe combined immunodeficiency due to CARD11 deficiency.

What condition is associated with CARD11 p.Asp629= (c.1887T>C)?

CARD11 p.Asp629= (c.1887T>C) is associated with severe combined immunodeficiency due to CARD11 deficiency, BENTA disease (ClinVar).

How common is CARD11 p.Asp629= (c.1887T>C) in the general population?

CARD11 p.Asp629= (c.1887T>C) is very rare (popmax 0.00449%, nfe) (gnomAD).

CARD11 p.Asp629=

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.1887T>C · rs150116627 · VCV540980

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

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 -0.8	GERP -4.2
Overall
CADD	5.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00449% European (non-Finnish) · 53/1,180,020 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00353% 57/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)grpmax	0.00449%	22,265

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp629=
Coding: c.1887T>C
MANE Select: NM_032415
dbSNP: rs150116627
Type: single nucleotide variant
Location: chr7:2924286 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 629: the 'inhibitory domain (id)' 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.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
CARD11 c.3019+5G>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-asp629 (accessed [today's date]).

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