Is CD19 p.Arg123Trp (c.367C>T) pathogenic?

CD19 p.Arg123Trp (c.367C>T) is classified Uncertain significance in CD19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-23). AlphaMissense: likely benign (0.2658); Very rare (popmax 0.00235%, eas).

How common is CD19 p.Arg123Trp (c.367C>T) in the general population?

CD19 p.Arg123Trp (c.367C>T) is very rare (popmax 0.00235%, eas) (gnomAD).

What do computational predictors say about CD19 p.Arg123Trp (c.367C>T)?

AlphaMissense predicts likely benign (score 0.2658) — an in-silico prediction, not a clinical call.

CD19 p.Arg123Trp

c.367C>T · rs1346128809 · VCV871885

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00235%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2658	likely benign
REVEL	0.317	indeterminate
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 2.3	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00235% East Asian · 1/42,530 alleles

Filtering AF 0.000381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000143%

Overall 0.00056% 8/1,428,048 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00235%	42,530
South Asian	0.0023%	43,556
European (non-Finnish)	0.00043%	232,627

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.Arg123Trp
Coding: c.367C>T
MANE Select: NM_001770
dbSNP: rs1346128809
Type: single nucleotide variant
Location: chr16:28932922 (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 123: a disulfide bond; a β-strand

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

Similar variants

CD19 p.Arg123Gln Uncertain significance ★ ⚠ same residue
CD19 c.835+3A>G Uncertain significance ★★ same type
CD19 p.Ala191Thr Uncertain significance ★★ ⚠ same type
CD19 p.Arg163His Uncertain significance ★★ ⚠ same type
CD19 p.Arg234Cys Uncertain significance ★★ ⚠ same type
CD19 p.Arg263His Uncertain significance ★★ ⚠ same type
CD19 p.Arg321Lys Uncertain significance ★★ ⚠ same type
CD19 p.Arg490Gln Uncertain significance ★★ ⚠ 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-arg123trp (accessed [today's date]).

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