Is CD19 p.Leu136= (c.406C>T) pathogenic?

CD19 p.Leu136= (c.406C>T) is classified Benign/Likely benign in CD19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Low-frequency (popmax 1.87%, eas); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Leu136= (c.406C>T)?

CD19 p.Leu136= (c.406C>T) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Leu136= (c.406C>T) in the general population?

CD19 p.Leu136= (c.406C>T) is low-frequency (popmax 1.87%, eas) (gnomAD).

CD19 p.Leu136=

c.406C>T · rs117769220 · VCV318802

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, eas)

Conditions

immunodeficiency, common variable, 3

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 1.3	phastCons 0.003
Overall
CADD	2.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.87% East Asian · 832/44,560 alleles

Filtering AF 1.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.72%

Overall 0.0567% 912/1,609,774 alleles · low-frequency exomes 810/1,457,548 · genomes 102/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.87%	54
Remaining individualsnot grpmax-eligible	0.0722%	1,385
South Asian	0.0321%	3,116
Middle Eastern	0.0165%	6,058
Admixed American	0.00168%	59,400
European (non-Finnish)	0.00034%	294,525

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: CD19
Protein: p.Leu136=
Coding: c.406C>T
MANE Select: NM_001770
dbSNP: rs117769220
Type: single nucleotide variant
Location: chr16:28932961 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.99 · 4 PDB

Full CD19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency, common variable, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD19 c.835+3A>G Uncertain significance ★★ same condition
CD19 p.Arg163His Uncertain significance ★★ ⚠ same condition
CD19 p.Arg263His Uncertain significance ★★ ⚠ same condition
CD19 p.Arg490Gln Uncertain significance ★★ ⚠ same condition
CD19 p.Arg76Ser Uncertain significance ★★ ⚠ same condition
CD19 p.Gln345His Uncertain significance ★★ ⚠ same condition
CD19 p.Glu21Gln Uncertain significance ★★ ⚠ same condition
CD19 p.Glu29Gln 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/cd19-p-leu136 (accessed [today's date]).

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