Is CARD11 p.Arg149= (c.447C>G) pathogenic?

CARD11 p.Arg149= (c.447C>G) is classified Likely benign in CARD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Very rare (popmax 0.00542%, nfe); Associated with BENTA disease.

What condition is associated with CARD11 p.Arg149= (c.447C>G)?

CARD11 p.Arg149= (c.447C>G) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How common is CARD11 p.Arg149= (c.447C>G) in the general population?

CARD11 p.Arg149= (c.447C>G) is very rare (popmax 0.00542%, nfe) (gnomAD).

How is BENTA disease inherited?

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

CARD11 p.Arg149=

c.447C>G · rs777043882 · VCV1492783

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00542%, nfe)

Conditions

BENTA disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -5.1
Overall
CADD	7.583	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00542% European (non-Finnish) · 64/1,180,046 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00397% 64/1,614,106 alleles · very rare

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.Arg149=
Coding: c.447C>G
dbSNP: rs777043882
Type: single nucleotide variant
Location: chr7:2944449 (GRCh38)

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

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-arg149 (accessed [today's date]).

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