Is CARD11 p.Arg641= (c.1923G>A) pathogenic?

CARD11 p.Arg641= (c.1923G>A) is classified Benign/Likely benign in CARD11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 2.53%, afr); Associated with BENTA disease.

How common is CARD11 p.Arg641= (c.1923G>A) in the general population?

CARD11 p.Arg641= (c.1923G>A) is low-frequency (popmax 2.53%, afr) (gnomAD).

How is BENTA disease inherited?

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

CARD11 p.Arg641=

Q: What condition is associated with CARD11 p.Arg641= (c.1923G>A)?

CARD11 p.Arg641= (c.1923G>A) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency, immunodeficiency 11b with atopic dermatitis (ClinVar).

c.1923G>A · rs41405944 · VCV791707

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.53%, afr)

Conditions

BENTA disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2	GERP -4.2
Overall
CADD	9.804	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.53% African / African-American · 1,897/75,044 alleles

Filtering AF 2.43% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.39%

Overall 0.13% 2,101/1,614,170 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.53%	40
Middle Eastern	0.198%	505
Admixed American	0.157%	639
Remaining individualsnot grpmax-eligible	0.133%	753
Finnishnot grpmax-eligible	0.00625%	16,003
South Asian	0.00439%	22,770
European (non-Finnish)	0.000593%	168,576

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.Arg641=
Coding: c.1923G>A
MANE Select: NM_032415
dbSNP: rs41405944
Type: single nucleotide variant
Location: chr7:2924250 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 641: the 'inhibitory domain (id)' region

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 immunodeficiency 11b with atopic dermatitis

For BENTA disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

CARD11 p.Arg641Ser 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-arg641 (accessed [today's date]).

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