Is MALT1 p.Asp784Val (c.2351A>T) pathogenic?

MALT1 p.Asp784Val (c.2351A>T) is classified Uncertain significance in MALT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-26). AlphaMissense: likely benign (0.1001); Very rare (popmax 0.004%, afr); Associated with combined immunodeficiency due to MALT1 deficiency.

What condition is associated with MALT1 p.Asp784Val (c.2351A>T)?

MALT1 p.Asp784Val (c.2351A>T) is associated with combined immunodeficiency due to MALT1 deficiency (ClinVar).

How common is MALT1 p.Asp784Val (c.2351A>T) in the general population?

MALT1 p.Asp784Val (c.2351A>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about MALT1 p.Asp784Val (c.2351A>T)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

MALT1 p.Asp784Val

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.2351A>T · rs904452707 · VCV541509

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to MALT1 deficiency

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.3	GERP -2.8, phastCons 0.001
Regional constraint	o/e 0.80	unconstrained · MANE · 5,919 bp · p 0.0004 · regional, not allelic
Overall
CADD	15.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,044 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,981
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Asp784Val
Coding: c.2351A>T
MANE Select: NM_006785
dbSNP: rs904452707
Type: single nucleotide variant
Location: chr18:58747718 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI 0.64 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 27 PDB

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.Asp784_Phe790dup 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.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-asp784val (accessed [today's date]).

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