Is CARD11 p.Ser652= (c.1956G>A) pathogenic?

CARD11 p.Ser652= (c.1956G>A) is classified Likely benign in CARD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-06). Very rare (popmax 0.00448%, eas); Associated with BENTA disease.

What condition is associated with CARD11 p.Ser652= (c.1956G>A)?

CARD11 p.Ser652= (c.1956G>A) is associated with BENTA disease, severe combined immunodeficiency due to CARD11 deficiency (ClinVar).

How common is CARD11 p.Ser652= (c.1956G>A) in the general population?

CARD11 p.Ser652= (c.1956G>A) is very rare (popmax 0.00448%, eas) (gnomAD).

How is BENTA disease inherited?

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

CARD11 p.Ser652=

c.1956G>A · VCV4790169

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

BENTA disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -16	GERP -4.1
Overall
CADD	0.156	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,652 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000904%

Overall 0.00144% 23/1,598,390 alleles · very rare exomes 19/1,446,216 · genomes 4/152,174 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00448%	22,326
European (non-Finnish)	0.0017%	58,724
Remaining individualsnot grpmax-eligible	0.00161%	62,006

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.Ser652=
Coding: c.1956G>A
MANE Select: NM_032415
Type: single nucleotide variant
Location: chr7:2923318 (GRCh38)
Gene constraint: LOEUF 0.364 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.83 · 2 PDB
Residue 652: a modified residue (phosphoserine; by pkc/prkcb and pkc/prkcq); the 'inhibitory domain (id)' 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.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
CARD11 c.3019+5G>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-ser652 (accessed [today's date]).

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