Is CD19 p.Met16Thr (c.47T>C) pathogenic?

CD19 p.Met16Thr (c.47T>C) is classified Likely benign in CD19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-21). AlphaMissense: likely benign (0.1044); Very rare (popmax 0.00167%, amr); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Met16Thr (c.47T>C)?

CD19 p.Met16Thr (c.47T>C) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Met16Thr (c.47T>C) in the general population?

CD19 p.Met16Thr (c.47T>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD19 p.Met16Thr (c.47T>C)?

AlphaMissense predicts likely benign (score 0.1044) — an in-silico prediction, not a clinical call.

CD19 p.Met16Thr

c.47T>C · rs745681190 · VCV973629

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1044 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency, common variable, 3

Computational evidence

Protein change
AlphaMissense	0.1044	likely benign
REVEL	0.139	moderately benign-leaning
SaProt	LLR -5.33	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 -0.6
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	0.662	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 0.00167% Admixed American · 1/59,974 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000682% 11/1,613,800 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed Americangrpmax	0.00167%	59,974
European (non-Finnish)	0.000508%	196,660

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met16Thr
Coding: c.47T>C
MANE Select: NM_001770
dbSNP: rs745681190
Type: single nucleotide variant
Location: chr16:28932047 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.99 · 4 PDB

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 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
CD19 p.Glu29Gln 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-met16thr (accessed [today's date]).

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