Is MALT1 p.Cys209= (c.627C>T) pathogenic?

MALT1 p.Cys209= (c.627C>T) is classified Likely benign in MALT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-28). Ultra-rare (popmax 0.0121%, afr); Associated with combined immunodeficiency due to MALT1 deficiency.

What condition is associated with MALT1 p.Cys209= (c.627C>T)?

MALT1 p.Cys209= (c.627C>T) is associated with combined immunodeficiency due to MALT1 deficiency (ClinVar).

How common is MALT1 p.Cys209= (c.627C>T) in the general population?

MALT1 p.Cys209= (c.627C>T) is ultra-rare (popmax 0.0121%, afr) (gnomAD).

MALT1 p.Cys209=

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.627C>T · rs143781059 · VCV1980911

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, afr)

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 -0.64	GERP -4.5, phastCons 0.005
Overall
CADD	11.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% African / African-American · 9/74,468 alleles

Filtering AF 0.00627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0047%

Overall 0.000933% 15/1,607,048 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0121%	8,274
South Asian	0.00224%	44,739
European (non-Finnish)	0.00034%	294,449

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.Cys209=
Coding: c.627C>T
MANE Select: NM_006785
dbSNP: rs143781059
Type: single nucleotide variant
Location: chr18:58700569 (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 209: a β-strand

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.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
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-cys209 (accessed [today's date]).

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