Is CD19 p.Phe8Leu (c.24C>A) pathogenic?

CD19 p.Phe8Leu (c.24C>A) is classified Uncertain significance in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-28). AlphaMissense: ambiguous (0.5076); Very rare (popmax 0.00167%, amr); Associated with immunodeficiency, common variable, 3.

What condition is associated with CD19 p.Phe8Leu (c.24C>A)?

CD19 p.Phe8Leu (c.24C>A) is associated with immunodeficiency, common variable, 3 (ClinVar).

How common is CD19 p.Phe8Leu (c.24C>A) in the general population?

CD19 p.Phe8Leu (c.24C>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CD19 p.Phe8Leu (c.24C>A)?

AlphaMissense predicts ambiguous (score 0.5076) — an in-silico prediction, not a clinical call.

CD19 p.Phe8Leu

c.24C>A · rs1567503993 · VCV2439814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5076 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

immunodeficiency, common variable, 3

Computational evidence

Protein change
AlphaMissense	0.5076	ambiguous
REVEL	0.05	moderately benign-leaning
SaProt	LLR -3.99	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.79
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	7.21	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 · 1/60,010 alleles

Overall 6.84e-05% 1/1,461,844 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.Phe8Leu
Coding: c.24C>A
MANE Select: NM_001770
dbSNP: rs1567503993
Type: single nucleotide variant
Location: chr16:28932024 (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-phe8leu (accessed [today's date]).

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