Is CD19 p.Pro542Ser (c.1624C>T) pathogenic?

CD19 p.Pro542Ser (c.1624C>T) is classified Uncertain significance in CD19 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-03-14). AlphaMissense: likely benign (0.118); Very rare (popmax 0.00236%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD19 p.Pro542Ser (c.1624C>T)?

CD19 p.Pro542Ser (c.1624C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CD19 p.Pro542Ser (c.1624C>T) in the general population?

CD19 p.Pro542Ser (c.1624C>T) is very rare (popmax 0.00236%, sas) (gnomAD).

What do computational predictors say about CD19 p.Pro542Ser (c.1624C>T)?

AlphaMissense predicts likely benign (score 0.118) — an in-silico prediction, not a clinical call.

CD19 p.Pro542Ser

c.1624C>T · rs760461186 · VCV1702605

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.118 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00236%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.118	likely benign
REVEL	0.143	moderately benign-leaning
SaProt	LLR -6.42	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 2.2	phastCons 0.81
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	18.77	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 0.00236% South Asian · 2/84,572 alleles

Filtering AF 0.000393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000147%

Overall 0.000322% 5/1,554,982 alleles · very rare exomes 4/1,402,788 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00236%	42,286
Remaining individualsnot grpmax-eligible	0.00166%	60,232
African / African-American	0.00137%	73,248
European (non-Finnish)	8.71e-05%	1,148,615

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.Pro542Ser
Coding: c.1624C>T
MANE Select: NM_001770
dbSNP: rs760461186
Type: single nucleotide variant
Location: chr16:28938916 (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 542: the 'disordered' region

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-pro542ser (accessed [today's date]).

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