Is CD19 p.Arg5His (c.14G>A) pathogenic?

CD19 p.Arg5His (c.14G>A) is classified Uncertain significance in CD19 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1181); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with CD19 p.Arg5His (c.14G>A)?

CD19 p.Arg5His (c.14G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CD19 p.Arg5His (c.14G>A) in the general population?

CD19 p.Arg5His (c.14G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about CD19 p.Arg5His (c.14G>A)?

AlphaMissense predicts likely benign (score 0.1181) — an in-silico prediction, not a clinical call.

CD19 p.Arg5His

c.14G>A · rs781764596 · VCV1954715

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1181 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1181	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.01	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 1.3	phastCons 0.025
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	15.52	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 0.0107% African / African-American · 8/74,880 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00118% 19/1,613,852 alleles · ultra-rare exomes 14/1,461,786 · genomes 5/152,066 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,360
Admixed American	0.00334%	29,984
European (non-Finnish)	0.000763%	131,106

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.Arg5His
Coding: c.14G>A
MANE Select: NM_001770
dbSNP: rs781764596
Type: single nucleotide variant
Location: chr16:28932014 (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

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

Similar variants

CD19 p.Arg5Cys Conflicting classifications of pathogenicity ★ ⚠ 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.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-arg5his (accessed [today's date]).

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