Is CARD11 p.Arg555= (c.1665G>A) pathogenic?

CARD11 p.Arg555= (c.1665G>A) is classified Likely benign in CARD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-09). Absent from gnomAD v4.1; Associated with BENTA disease.

What condition is associated with CARD11 p.Arg555= (c.1665G>A)?

CARD11 p.Arg555= (c.1665G>A) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How common is CARD11 p.Arg555= (c.1665G>A) in the general population?

CARD11 p.Arg555= (c.1665G>A) is absent from gnomAD v4.1 (gnomAD).

How is BENTA disease inherited?

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

CARD11 p.Arg555=

c.1665G>A · rs2115053830 · VCV2937259

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -1.4	GERP -2.3
Overall
CADD	8.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CARD11
Protein: p.Arg555=
Coding: c.1665G>A
MANE Select: NM_032415
dbSNP: rs2115053830
Type: single nucleotide variant
Location: chr7:2928687 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 555: the 'inhibitory domain (id)' region; the 'disordered' 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

For BENTA disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy

Similar variants

CARD11 p.Arg555Gly Uncertain significance ★ ⚠ same residue
CARD11 p.Arg555Trp Uncertain significance ★ ⚠ same residue
CARD11 p.Arg555Gln Likely benign ★ same residue
CARD11 p.Arg555fs Pathogenic ★ 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

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-arg555 (accessed [today's date]).

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