Is CBR4 p.Ala19Val (c.56C>T) pathogenic?

CBR4 p.Ala19Val (c.56C>T) is classified Uncertain significance in CBR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.3344); Absent from gnomAD v4.1.

How common is CBR4 p.Ala19Val (c.56C>T) in the general population?

CBR4 p.Ala19Val (c.56C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBR4 p.Ala19Val (c.56C>T)?

AlphaMissense predicts likely benign (score 0.3344) — an in-silico prediction, not a clinical call.

CBR4 p.Ala19Val

c.56C>T · rs2534649668 · VCV2530931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3344 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3344	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -9.42	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 20 kb · p 0.35 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

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: CBR4
Protein: p.Ala19Val
Coding: c.56C>T
MANE Select: NM_032783
dbSNP: rs2534649668
Type: single nucleotide variant
Location: chr4:169010034 (GRCh38)
Gene constraint: LOEUF 1.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 2 PDB
Residue 19: an α-helix

Full CBR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PALLD c.2199+4C>T Uncertain significance ★★ same type
PALLD c.*110G>C Uncertain significance ★★ same type
PALLD c.*127C>G Uncertain significance ★★ same type
PALLD c.*135C>T Uncertain significance ★★ same type
PALLD c.*155C>G Uncertain significance ★★ same type
PALLD c.*161C>T Uncertain significance ★★ same type
PALLD c.*182T>A Uncertain significance ★★ same type
PALLD c.*194G>C 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/cbr4-p-ala19val (accessed [today's date]).

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