Is CD19 p.Val472Phe (c.1414G>T) pathogenic?

CD19 p.Val472Phe (c.1414G>T) is classified Uncertain significance in CD19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely benign (0.1711); Very rare (popmax 0.00333%, amr).

How common is CD19 p.Val472Phe (c.1414G>T) in the general population?

CD19 p.Val472Phe (c.1414G>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CD19 p.Val472Phe (c.1414G>T)?

AlphaMissense predicts likely benign (score 0.1711) — an in-silico prediction, not a clinical call.

CD19 p.Val472Phe

c.1414G>T · rs1224098003 · VCV1920790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1711 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1711	likely benign
REVEL	0.18	moderately benign-leaning
SaProt	LLR -7.60	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 6.6	phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 6,959 bp · p 0.00041 · regional, not allelic
Overall
CADD	24.6	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 0.00333% Admixed American · 2/59,982 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,613,942 alleles · very rare

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.Val472Phe
Coding: c.1414G>T
MANE Select: NM_001770
dbSNP: rs1224098003
Type: single nucleotide variant
Location: chr16:28937665 (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 472: the 'disordered' region

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

Similar variants

CD19 p.Val472= 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
CD19 p.Arg321Lys 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-val472phe (accessed [today's date]).

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