Is CD19 p.Asn463fs (c.1386_1387del) pathogenic?

CD19 p.Asn463fs (c.13861387del) is classified Pathogenic in CD19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2006-05-04). Very rare (popmax 0.005%, amr); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Asn463fs (c.1386_1387del)?

CD19 p.Asn463fs (c.1386_1387del) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Asn463fs (c.1386_1387del) in the general population?

CD19 p.Asn463fs (c.1386_1387del) is very rare (popmax 0.005%, amr) (gnomAD).

CD19 p.Asn463fs

c.1386_1387del · rs1393707607 · VCV18055

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

immunodeficiency, common variable, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.5
Overall
CADD	34.0	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 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Remaining individualsnot grpmax-eligible	0.0032%	31,252

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.Asn463fs
Coding: c.1386_1387del
MANE Select: NM_001770
dbSNP: rs1393707607
Type: Microsatellite
Location: chr16:28937635 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.99 · 4 PDB
Residue 463: the 'disordered' region

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 p.Asn463= Likely benign ★ same residue
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

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-asn463fs (accessed [today's date]).

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