Is CD19 p.Ala253Val (c.758C>T) pathogenic?

CD19 p.Ala253Val (c.758C>T) is classified Uncertain significance in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). AlphaMissense: likely benign (0.1118); Absent from gnomAD v4.1.

How common is CD19 p.Ala253Val (c.758C>T) in the general population?

CD19 p.Ala253Val (c.758C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD19 p.Ala253Val (c.758C>T)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

CD19 p.Ala253Val

c.758C>T · rs2506461549 · VCV1978510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.21
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	12.22	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD19
Protein: p.Ala253Val
Coding: c.758C>T
MANE Select: NM_001770
dbSNP: rs2506461549
Type: single nucleotide variant
Location: chr16:28933432 (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 253: the ig-like c2-type 2 domain; an α-helix

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-ala253val (accessed [today's date]).

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