Is CD19 p.Leu174Val (c.520C>G) pathogenic?

CD19 p.Leu174Val (c.520C>G) is classified Benign/Likely benign in CD19 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.06); Common (popmax 94.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Leu174Val (c.520C>G)?

CD19 p.Leu174Val (c.520C>G) is associated with immunodeficiency, common variable, 3 (ClinVar).

What do computational predictors say about CD19 p.Leu174Val (c.520C>G)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

CD19 p.Leu174Val

Q: How common is CD19 p.Leu174Val (c.520C>G) in the general population?

CD19 p.Leu174Val (c.520C>G) is common (popmax 94.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.520C>G · rs2904880 · VCV318803

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 94.6%, afr) — 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	0.06	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.31	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 0.79	phastCons 0.13
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	1.404	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 94.6% African / African-American · 70,923/74,966 alleles

Filtering AF 94% ClinGen BA1/BS1 input FAF95, joint · FAF99 93.8%

Overall 70.3% 1,134,331/1,612,920 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	94.6%	1
East Asian	90.8%	1
Middle Eastern	83.3%	1
South Asian	82.2%	1
Amishnot grpmax-eligible	80.4%	1
Ashkenazi Jewishnot grpmax-eligible	76.6%	1
Remaining individualsnot grpmax-eligible	72.8%	1
Finnishnot grpmax-eligible	68.3%	1
European (non-Finnish)	67.5%	1
Admixed American	57.4%	2

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.Leu174Val
Coding: c.520C>G
MANE Select: NM_001770
dbSNP: rs2904880
Type: single nucleotide variant
Location: chr16:28933075 (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 174: a disulfide bond; a UniProt-annotated variant site (in)

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.Leu174= Likely benign ★ 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-leu174val (accessed [today's date]).

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