Is CARD11 p.Arg855Pro (c.2564G>C) pathogenic?

CARD11 p.Arg855Pro (c.2564G>C) is classified Uncertain significance in CARD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: ambiguous (0.3951); Absent from gnomAD v4.1; Associated with severe combined immunodeficiency due to CARD11 deficiency.

What condition is associated with CARD11 p.Arg855Pro (c.2564G>C)?

CARD11 p.Arg855Pro (c.2564G>C) is associated with severe combined immunodeficiency due to CARD11 deficiency, BENTA disease (ClinVar).

How common is CARD11 p.Arg855Pro (c.2564G>C) in the general population?

CARD11 p.Arg855Pro (c.2564G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CARD11 p.Arg855Pro (c.2564G>C)?

AlphaMissense predicts ambiguous (score 0.3951) — an in-silico prediction, not a clinical call.

CARD11 p.Arg855Pro

Q: How is Combined immunodeficiency due to CARD11 deficiency inherited?

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

c.2564G>C · rs928782717 · VCV2949764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3951 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,551,464)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

severe combined immunodeficiency due to CARD11 deficiency

Computational evidence

Protein change
AlphaMissense	0.3951	ambiguous
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.53	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 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 31 kb · p 2.9e-06 · regional, not allelic
Overall
CADD	23.9	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

No allele count reported in gnomAD v4.1 (AN 1,551,464). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CARD11
Protein: p.Arg855Pro
Coding: c.2564G>C
MANE Select: NM_032415
dbSNP: rs928782717
Type: single nucleotide variant
Location: chr7:2918534 (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

severe combined immunodeficiency due to CARD11 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: BENTA disease

For Combined immunodeficiency due to CARD11 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CARD11 p.Arg855Gln Uncertain significance ★★ ⚠ same residue
CARD11 p.Arg855= Likely benign ★★ 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-arg855pro (accessed [today's date]).

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