Is CD19 p.Arg514His (c.1541G>A) pathogenic?

CD19 p.Arg514His (c.1541G>A) is classified Benign/Likely benign in CD19 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0864); Common (popmax 6.69%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Arg514His (c.1541G>A)?

CD19 p.Arg514His (c.1541G>A) is associated with immunodeficiency, common variable, 3 (ClinVar).

What do computational predictors say about CD19 p.Arg514His (c.1541G>A)?

AlphaMissense predicts likely benign (score 0.0864) — an in-silico prediction, not a clinical call.

CD19 p.Arg514His

Q: How common is CD19 p.Arg514His (c.1541G>A) in the general population?

CD19 p.Arg514His (c.1541G>A) is common (popmax 6.69%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1541G>A · rs34763945 · VCV318811

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0864 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.69%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency, common variable, 3

Computational evidence

Protein change
AlphaMissense	0.0864	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -7.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	phastCons 0.24
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	18.98	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.69% European (non-Finnish) · 78,926/1,179,742 alleles

Filtering AF 6.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.63%

Overall 5.66% 91,312/1,613,794 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	6.69%	15
Finnishnot grpmax-eligible	6.44%	16
Remaining individualsnot grpmax-eligible	5.41%	18
South Asian	2.29%	44
Admixed American	2.21%	45
Ashkenazi Jewishnot grpmax-eligible	2.02%	50
Middle Eastern	1.93%	52
Amishnot grpmax-eligible	1.54%	65
African / African-American	0.99%	101
East Asian	0.0111%	8,978

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.Arg514His
Coding: c.1541G>A
MANE Select: NM_001770
dbSNP: rs34763945
Type: single nucleotide variant
Location: chr16:28938730 (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 514: a UniProt-annotated variant site (in); 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.Arg514Cys 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-arg514his (accessed [today's date]).

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