Is CD19 p.Pro57= (c.171G>A) pathogenic?

CD19 p.Pro57= (c.171G>A) is classified Conflicting classifications of pathogenicity in CD19 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-24). Rare (popmax 0.103%, sas); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Pro57= (c.171G>A)?

CD19 p.Pro57= (c.171G>A) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Pro57= (c.171G>A) in the general population?

CD19 p.Pro57= (c.171G>A) is rare (popmax 0.103%, sas) (gnomAD).

CD19 p.Pro57=

c.171G>A · rs199665700 · VCV318797

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.103%, sas)

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 1.6	phastCons 0.002
Overall
CADD	9.167	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.103% South Asian · 94/91,066 alleles

Filtering AF 0.0863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0801%

Overall 0.015% 242/1,614,046 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.103%	969
Middle Eastern	0.0498%	2,007
East Asian	0.0379%	2,639
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.00907%	11,028
African / African-American	0.004%	25,012
Finnishnot grpmax-eligible	0.00312%	32,017
Admixed American	0.00167%	60,016

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.Pro57=
Coding: c.171G>A
MANE Select: NM_001770
dbSNP: rs199665700
Type: single nucleotide variant
Location: chr16:28932428 (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 57: a disulfide bond; the ig-like c2-type 1 domain

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.Pro57Leu Uncertain significance ★★ ⚠ 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-pro57 (accessed [today's date]).

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