Is CD19 p.Phe94fs (c.278dup) pathogenic?

CD19 p.Phe94fs (c.278dup) is classified Pathogenic in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-10). Very rare (popmax 0.000339%, nfe).

How common is CD19 p.Phe94fs (c.278dup) in the general population?

CD19 p.Phe94fs (c.278dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

CD19 p.Phe94fs

c.278dup · rs1250118764 · VCV1927283

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 2 of 15
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,978 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,838 alleles · very rare

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.Phe94fs
Coding: c.278dup
MANE Select: NM_001770
dbSNP: rs1250118764
Type: Duplication
Location: chr16:28932529 (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 94: a disulfide bond; the ig-like c2-type 1 domain; a β-strand

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

Similar variants

CD19 p.Arg549fs Uncertain significance ★ same type
CD19 p.Pro204_Asp205insPro Uncertain significance ★ same type
CD19 c.1303+18dup Benign ★ same type
CD19 c.89-12_89-3dup Likely benign ★ same type
CD19 c.89-9dup Likely benign ★ same type
CD19 p.Arg325fs Pathogenic same type

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-phe94fs (accessed [today's date]).

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