Is CBLB p.Val196= (c.588A>T) pathogenic?

CBLB p.Val196= (c.588A>T) is classified Likely benign in CBLB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-26). Very rare (popmax 0.00839%, nfe); Associated with CBLB-related disorder.

What condition is associated with CBLB p.Val196= (c.588A>T)?

CBLB p.Val196= (c.588A>T) is associated with CBLB-related disorder (ClinVar).

How common is CBLB p.Val196= (c.588A>T) in the general population?

CBLB p.Val196= (c.588A>T) is very rare (popmax 0.00839%, nfe) (gnomAD).

CBLB p.Val196=

c.588A>T · rs748996723 · VCV3053848

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00839%, nfe)

Conditions

CBLB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.073	GERP -5.6, phastCons 0.82
Overall
CADD	4.974	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00839% European (non-Finnish) · 99/1,179,580 alleles

Filtering AF 0.00703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00652%

Overall 0.00632% 102/1,613,506 alleles · very rare exomes 99/1,461,296 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00839%	11,915
Remaining individualsnot grpmax-eligible	0.0048%	20,825

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: CBLB
Protein: p.Val196=
Coding: c.588A>T
MANE Select: NM_170662
dbSNP: rs748996723
Type: single nucleotide variant
Location: chr3:105751597 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 196: the cbl-ptb domain; the 'ef-hand-like' region; an α-helix

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

Disease context

CBLB-related disorder

Similar variants

CBLB p.Ala621= Benign same condition
CBLB p.Arg570= Likely benign same condition
CBLB p.Asn466Asp Benign same condition
CBLB p.Asn883Asp Benign same condition
CBLB p.Asp351= Benign same condition
CBLB p.Asp424= Benign same condition
CBLB p.Leu447= Benign same condition
CBLB p.Lys275= Benign 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/cblb-p-val196 (accessed [today's date]).

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