Is CARD11 p.Arg404= (c.1212G>A) pathogenic?

CARD11 p.Arg404= (c.1212G>A) is classified Benign in CARD11 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). Common (popmax 6.86%, amr) — too common for a highly-penetrant pathogenic allele; Associated with BENTA disease.

What condition is associated with CARD11 p.Arg404= (c.1212G>A)?

CARD11 p.Arg404= (c.1212G>A) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How is BENTA disease inherited?

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

CARD11 p.Arg404=

Q: How common is CARD11 p.Arg404= (c.1212G>A) in the general population?

CARD11 p.Arg404= (c.1212G>A) is common (popmax 6.86%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1212G>A · rs142108678 · VCV434567

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.86%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

BENTA disease

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 0.47	GERP -4, phastCons 1
Overall
CADD	8.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.86% Admixed American · 4,119/60,032 alleles

Filtering AF 6.69% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.62%

Overall 0.268% 4,319/1,614,272 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	6.86%	15
Remaining individualsnot grpmax-eligible	0.178%	563
African / African-American	0.0773%	1,294
East Asian	0.0379%	2,641
European (non-Finnish)	0.00119%	84,289

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.Arg404=
Coding: c.1212G>A
MANE Select: NM_032415
dbSNP: rs142108678
Type: single nucleotide variant
Location: chr7:2937166 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB

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

Disease context

BENTA disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency due to CARD11 deficiency

For BENTA disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

CARD11 p.Arg404Gly 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-arg404 (accessed [today's date]).

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