Is CD19 p.Glu165Asp (c.495G>T) pathogenic?

CD19 p.Glu165Asp (c.495G>T) is classified Uncertain significance in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-14). AlphaMissense: likely benign (0.3102); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CD19 p.Glu165Asp (c.495G>T)?

CD19 p.Glu165Asp (c.495G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD19 p.Glu165Asp (c.495G>T) in the general population?

CD19 p.Glu165Asp (c.495G>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CD19 p.Glu165Asp (c.495G>T)?

AlphaMissense predicts likely benign (score 0.3102) — an in-silico prediction, not a clinical call.

CD19 p.Glu165Asp

c.495G>T · rs753721854 · VCV3140370

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3102	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -9.27	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 2.9	phastCons 0.31
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	14.93	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 0.000169% European (non-Finnish) · 2/1,179,994 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,652 alleles · very rare

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.Glu165Asp
Coding: c.495G>T
MANE Select: NM_001770
dbSNP: rs753721854
Type: single nucleotide variant
Location: chr16:28933050 (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 165: a disulfide bond; a β-strand

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.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
CD19 p.Gly438Ser 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-glu165asp (accessed [today's date]).

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