Is CD19 p.Ser127= (c.381G>A) pathogenic?

CD19 p.Ser127= (c.381G>A) is classified Benign/Likely benign in CD19 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.789%, nfe); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Ser127= (c.381G>A)?

CD19 p.Ser127= (c.381G>A) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Ser127= (c.381G>A) in the general population?

CD19 p.Ser127= (c.381G>A) is rare (popmax 0.789%, nfe) (gnomAD).

CD19 p.Ser127=

c.381G>A · rs142342927 · VCV318798

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.789%, nfe)

Conditions

immunodeficiency, common variable, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.064	phastCons 0.1
Overall
CADD	13.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.789% European (non-Finnish) · 9,233/1,170,046 alleles

Filtering AF 0.776% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.77%

Overall 0.662% 10,544/1,593,238 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.835%	120
European (non-Finnish)grpmax	0.789%	127
Middle Eastern	0.613%	163
Remaining individualsnot grpmax-eligible	0.54%	185
Amishnot grpmax-eligible	0.33%	303
African / African-American	0.261%	383
Admixed American	0.179%	559
Ashkenazi Jewishnot grpmax-eligible	0.103%	972
South Asian	0.101%	993

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser127=
Coding: c.381G>A
MANE Select: NM_001770
dbSNP: rs142342927
Type: single nucleotide variant
Location: chr16:28932936 (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 127: a disulfide bond

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-ser127 (accessed [today's date]).

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