Is CARD11 p.Arg855= (c.2563C>A) pathogenic?

CARD11 p.Arg855= (c.2563C>A) is classified Likely benign in CARD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-15). Very rare (popmax 0.00209%, nfe); Associated with BENTA disease.

What condition is associated with CARD11 p.Arg855= (c.2563C>A)?

CARD11 p.Arg855= (c.2563C>A) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How common is CARD11 p.Arg855= (c.2563C>A) in the general population?

CARD11 p.Arg855= (c.2563C>A) is very rare (popmax 0.00209%, nfe) (gnomAD).

How is BENTA disease inherited?

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

CARD11 p.Arg855=

c.2563C>A · rs772266095 · VCV2925285

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00209%, nfe)

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 5.3	GERP 1.7, phastCons 1
Overall
CADD	10.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00209% European (non-Finnish) · 24/1,147,098 alleles

Filtering AF 0.00142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00161% 25/1,551,322 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00209%	47,796
Remaining individualsnot grpmax-eligible	0.00166%	60,100

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.Arg855=
Coding: c.2563C>A
MANE Select: NM_032415
dbSNP: rs772266095
Type: single nucleotide variant
Location: chr7:2918535 (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.Arg855Gln Uncertain significance ★★ ⚠ same residue
CARD11 p.Arg855Pro Uncertain significance ★ ⚠ same residue
CARD11 p.Arg855Trp 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

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-arg855 (accessed [today's date]).

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