Is CD19 p.Ser454= (c.1362C>T) pathogenic?

CD19 p.Ser454= (c.1362C>T) is classified Likely benign in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). Very rare (popmax 0.00364%, nfe).

How common is CD19 p.Ser454= (c.1362C>T) in the general population?

CD19 p.Ser454= (c.1362C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

CD19 p.Ser454=

c.1362C>T · rs756350072 · VCV744232

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	phastCons 1
Overall
CADD	9.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,180,016 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00273% 44/1,614,008 alleles · very rare exomes 43/1,461,878 · genomes 1/152,130 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,442
African / African-American	0.00133%	74,924

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.Ser454=
Coding: c.1362C>T
MANE Select: NM_001770
dbSNP: rs756350072
Type: single nucleotide variant
Location: chr16:28937513 (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 454: the 'disordered' region

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

Similar variants

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
CD19 p.Arg321Lys Uncertain significance ★★ ⚠ same type
CD19 p.Arg490Gln 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-ser454 (accessed [today's date]).

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