Is CD19 p.Thr374Ser (c.1121C>G) pathogenic?

CD19 p.Thr374Ser (c.1121C>G) is classified Uncertain significance in CD19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-06). AlphaMissense: likely benign (0.1043); Ultra-rare (popmax 0.0657%, amr); Associated with Inborn genetic diseases.

What condition is associated with CD19 p.Thr374Ser (c.1121C>G)?

CD19 p.Thr374Ser (c.1121C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CD19 p.Thr374Ser (c.1121C>G) in the general population?

CD19 p.Thr374Ser (c.1121C>G) is ultra-rare (popmax 0.0657%, amr) (gnomAD).

What do computational predictors say about CD19 p.Thr374Ser (c.1121C>G)?

AlphaMissense predicts likely benign (score 0.1043) — an in-silico prediction, not a clinical call.

CD19 p.Thr374Ser

c.1121C>G · rs1476550159 · VCV2054666

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1043 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1043	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -5.76	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 1.4	phastCons 0.001
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	8.861	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 0.0657% Admixed American · 36/54,828 alleles

Filtering AF 0.0487% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0428%

Overall 0.0027% 43/1,594,472 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0657%	1,523
Remaining individualsnot grpmax-eligible	0.00162%	61,878
European (non-Finnish)	0.000512%	195,490

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.Thr374Ser
Coding: c.1121C>G
MANE Select: NM_001770
dbSNP: rs1476550159
Type: single nucleotide variant
Location: chr16:28937059 (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 374: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD19 p.Thr374= Likely benign ★★ same residue
CD19 p.Arg234Cys Uncertain significance ★★ ⚠ same condition
CD19 p.Arg321Lys Uncertain significance ★★ ⚠ same condition
CD19 p.Arg549Cys Uncertain significance ★★ ⚠ same condition
CD19 p.Arg549Leu Uncertain significance ★★ ⚠ same condition
CD19 p.Arg54Trp Uncertain significance ★★ ⚠ same condition
CD19 p.Arg5His Uncertain significance ★★ ⚠ same condition
CD19 p.Asp538Asn 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-thr374ser (accessed [today's date]).

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