Is MALT1 p.Arg296Ter (c.886C>T) pathogenic?

MALT1 p.Arg296Ter (c.886C>T) is classified Likely pathogenic in MALT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-31). Very rare (popmax 8.48e-05%, nfe); Associated with combined immunodeficiency due to MALT1 deficiency.

What condition is associated with MALT1 p.Arg296Ter (c.886C>T)?

MALT1 p.Arg296Ter (c.886C>T) is associated with combined immunodeficiency due to MALT1 deficiency (ClinVar).

How common is MALT1 p.Arg296Ter (c.886C>T) in the general population?

MALT1 p.Arg296Ter (c.886C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MALT1 p.Arg296Ter

Q: How is Combined immunodeficiency due to MALT1 deficiency inherited?

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

c.886C>T · VCV3583378

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

combined immunodeficiency due to MALT1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 17
Splicing
SpliceAI	Δ0.42	donor loss · deltas
Pangolin	Δ0.52	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP 2.3, phastCons 0.98
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,178,756 alleles

Overall 0.000658% 1/152,058 alleles · very rare

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: MALT1
Protein: p.Arg296Ter
Coding: c.886C>T
MANE Select: NM_006785
Type: single nucleotide variant
Location: chr18:58710033 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.64 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 27 PDB
Residue 296: the ig-like c2-type 2 domain

Full MALT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to MALT1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to MALT1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

MALT1 p.Arg296Gln Uncertain significance ★★ ⚠ same residue
MALT1 p.Arg191Ter Pathogenic ★★ same condition
MALT1 c.1753+5G>A Uncertain significance ★★ same condition
MALT1 p.Ala413Val Uncertain significance ★★ ⚠ same condition
MALT1 p.Ala774Pro Uncertain significance ★★ ⚠ same condition
MALT1 p.Ala791Thr Uncertain significance ★★ ⚠ same condition
MALT1 p.Arg149Gln Uncertain significance ★★ ⚠ same condition
MALT1 p.Arg354Pro 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/malt1-p-arg296ter (accessed [today's date]).

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