Is CBLB p.Asn466Asp (c.1396A>G) pathogenic?

CBLB p.Asn466Asp (c.1396A>G) is classified Benign in CBLB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-03-20). AlphaMissense: likely benign (0.2503); Low-frequency (popmax 3.62%, eas); Associated with CBLB-related disorder.

What condition is associated with CBLB p.Asn466Asp (c.1396A>G)?

CBLB p.Asn466Asp (c.1396A>G) is associated with CBLB-related disorder (ClinVar).

How common is CBLB p.Asn466Asp (c.1396A>G) in the general population?

CBLB p.Asn466Asp (c.1396A>G) is low-frequency (popmax 3.62%, eas) (gnomAD).

What do computational predictors say about CBLB p.Asn466Asp (c.1396A>G)?

AlphaMissense predicts likely benign (score 0.2503) — an in-silico prediction, not a clinical call.

CBLB p.Asn466Asp

c.1396A>G · rs61758360 · VCV133818

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2503 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.62%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CBLB-related disorder

Computational evidence

Protein change
AlphaMissense	0.2503	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -6.17	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 2.1, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 164 kb · p 3.4e-12 · regional, not allelic
Overall
CADD	20.1	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

Grpmax group 3.62% East Asian · 1,624/44,874 alleles

Filtering AF 3.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.41%

Overall 0.112% 1,809/1,613,612 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.62%	28
Remaining individualsnot grpmax-eligible	0.168%	595
South Asian	0.0538%	1,859
Middle Eastern	0.0165%	6,060
Admixed American	0.0133%	7,497
African / African-American	0.004%	25,005
European (non-Finnish)	0.00161%	62,083

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.Asn466Asp
Coding: c.1396A>G
MANE Select: NM_170662
dbSNP: rs61758360
Type: single nucleotide variant
Location: chr3:105720058 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 466: the 'disordered' region

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.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
CBLB p.Pro280= 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-asn466asp (accessed [today's date]).

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