Is CD19 p.Asn457= (c.1371C>T) pathogenic?

CD19 p.Asn457= (c.1371C>T) is classified Conflicting classifications of pathogenicity in CD19 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-14). Ultra-rare (popmax 0.0275%, nfe); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Asn457= (c.1371C>T)?

CD19 p.Asn457= (c.1371C>T) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Asn457= (c.1371C>T) in the general population?

CD19 p.Asn457= (c.1371C>T) is ultra-rare (popmax 0.0275%, nfe) (gnomAD).

CD19 p.Asn457=

c.1371C>T · rs199570434 · VCV318810

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, nfe)

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 -5.1
Overall
CADD	0.737	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% European (non-Finnish) · 325/1,179,986 alleles

Filtering AF 0.025% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.0205% 331/1,614,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0275%	3,631
East Asian	0.00446%	22,435
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Finnishnot grpmax-eligible	0.00156%	64,026
African / African-American	0.00133%	75,010

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.Asn457=
Coding: c.1371C>T
MANE Select: NM_001770
dbSNP: rs199570434
Type: single nucleotide variant
Location: chr16:28937522 (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 457: 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 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-asn457 (accessed [today's date]).

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