Is CD19 p.Val318Ala (c.953T>C) pathogenic?

CD19 p.Val318Ala (c.953T>C) is classified Uncertain significance in CD19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.1963); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with CD19 p.Val318Ala (c.953T>C)?

CD19 p.Val318Ala (c.953T>C) is associated with Inborn genetic diseases (ClinVar).

How common is CD19 p.Val318Ala (c.953T>C) in the general population?

CD19 p.Val318Ala (c.953T>C) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about CD19 p.Val318Ala (c.953T>C)?

AlphaMissense predicts likely benign (score 0.1963) — an in-silico prediction, not a clinical call.

CD19 p.Val318Ala

c.953T>C · rs761197862 · VCV1448799

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1963 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1963	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.22	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 0.12
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	14.83	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00533% 86/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Admixed American	0.00833%	12,001
European (non-Finnish)	0.00661%	15,128
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Val318Ala
Coding: c.953T>C
MANE Select: NM_001770
dbSNP: rs761197862
Type: single nucleotide variant
Location: chr16:28936159 (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.Val318= Likely benign ★ 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.Arg5His Uncertain significance ★★ ⚠ same condition
CD19 p.Asp538Asn 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-val318ala (accessed [today's date]).

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