Is CD19 p.Tyr461Cys (c.1382A>G) pathogenic?

CD19 p.Tyr461Cys (c.1382A>G) is classified Uncertain significance in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). AlphaMissense: ambiguous (0.5269); Very rare (popmax 0.00373%, nfe).

How common is CD19 p.Tyr461Cys (c.1382A>G) in the general population?

CD19 p.Tyr461Cys (c.1382A>G) is very rare (popmax 0.00373%, nfe) (gnomAD).

What do computational predictors say about CD19 p.Tyr461Cys (c.1382A>G)?

AlphaMissense predicts ambiguous (score 0.5269) — an in-silico prediction, not a clinical call.

CD19 p.Tyr461Cys

c.1382A>G · rs1211081319 · VCV1410107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5269	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -10.31	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	25.9	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 0.00373% European (non-Finnish) · 44/1,179,998 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00291% 47/1,613,938 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,818
Remaining individualsnot grpmax-eligible	0.0032%	31,242
African / African-American	0.00134%	74,860

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.Tyr461Cys
Coding: c.1382A>G
MANE Select: NM_001770
dbSNP: rs1211081319
Type: single nucleotide variant
Location: chr16:28937633 (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 461: the 'disordered' region

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

Similar variants

CD19 p.Tyr461Phe Uncertain significance ★ ⚠ same residue
CD19 p.Tyr461= Likely benign ★ same residue
CD19 c.835+3A>G Uncertain significance ★★ same type
CD19 p.Ala191Thr Uncertain significance ★★ ⚠ same type
CD19 p.Arg123Trp Uncertain significance ★★ ⚠ same type
CD19 p.Arg163His Uncertain significance ★★ ⚠ same type
CD19 p.Arg234Cys Uncertain significance ★★ ⚠ same type
CD19 p.Arg263His Uncertain significance ★★ ⚠ same type

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-tyr461cys (accessed [today's date]).

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