Is MALT1 p.Leu554= (c.1662A>G) pathogenic?

MALT1 p.Leu554= (c.1662A>G) is classified Likely benign in MALT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). Absent from gnomAD v4.1; Associated with combined immunodeficiency due to MALT1 deficiency.

What condition is associated with MALT1 p.Leu554= (c.1662A>G)?

MALT1 p.Leu554= (c.1662A>G) is associated with combined immunodeficiency due to MALT1 deficiency (ClinVar).

How common is MALT1 p.Leu554= (c.1662A>G) in the general population?

MALT1 p.Leu554= (c.1662A>G) is absent from gnomAD v4.1 (gnomAD).

MALT1 p.Leu554=

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.1662A>G · rs765652691 · VCV2849918

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,571,230)

Conditions

combined immunodeficiency due to MALT1 deficiency

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 0.11	GERP -5.2, phastCons 0.28
Overall
CADD	6.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,571,230). 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: MALT1
Protein: p.Leu554=
Coding: c.1662A>G
MANE Select: NM_006785
dbSNP: rs765652691
Type: single nucleotide variant
Location: chr18:58741923 (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 554: the 'caspase-like' region

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.Leu554delinsPhePhePhePhePhePheXaaXaaXaaXaaAlaGlyArgLeuGlnTer Pathogenic ★ 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.Arg296Gln 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-leu554 (accessed [today's date]).

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