Is CARD11 p.Ser293Arg (c.879C>G) pathogenic?

CARD11 p.Ser293Arg (c.879C>G) is classified Uncertain significance in CARD11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: ambiguous (0.5446); Very rare (popmax 0.00167%, amr); Associated with BENTA disease.

What condition is associated with CARD11 p.Ser293Arg (c.879C>G)?

CARD11 p.Ser293Arg (c.879C>G) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How common is CARD11 p.Ser293Arg (c.879C>G) in the general population?

CARD11 p.Ser293Arg (c.879C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

How is BENTA disease inherited?

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

What do computational predictors say about CARD11 p.Ser293Arg (c.879C>G)?

AlphaMissense predicts ambiguous (score 0.5446) — an in-silico prediction, not a clinical call.

CARD11 p.Ser293Arg

c.879C>G · VCV3754118

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5446 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

BENTA disease

Computational evidence

Protein change
AlphaMissense	0.5446	ambiguous
REVEL	0.184	benign-leaning
SaProt	LLR -7.21	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -0.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 1,109 bp · p 0.13 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,008 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,592 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,008
Finnishnot grpmax-eligible	0.00157%	63,814
European (non-Finnish)	0.000169%	589,984

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.Ser293Arg
Coding: c.879C>G
MANE Select: NM_032415
Type: single nucleotide variant
Location: chr7:2938817 (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.Ser293= Likely benign ★★ 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-ser293arg (accessed [today's date]).

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