Is CBLB p.Lys275= (c.825A>G) pathogenic?

CBLB p.Lys275= (c.825A>G) is classified Benign in CBLB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). Rare (popmax 0.723%, afr); Associated with CBLB-related disorder.

What condition is associated with CBLB p.Lys275= (c.825A>G)?

CBLB p.Lys275= (c.825A>G) is associated with CBLB-related disorder (ClinVar).

How common is CBLB p.Lys275= (c.825A>G) in the general population?

CBLB p.Lys275= (c.825A>G) is rare (popmax 0.723%, afr) (gnomAD).

CBLB p.Lys275=

c.825A>G · rs116564819 · VCV3037193

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.723%, afr)

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 -0.51	GERP -4.3, phastCons 0.11
Overall
CADD	3.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.723% African / African-American · 542/75,004 alleles

Filtering AF 0.672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.652%

Overall 0.0373% 602/1,612,224 alleles · rare exomes 301/1,459,880 · genomes 301/152,344 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.723%	138
Remaining individualsnot grpmax-eligible	0.0449%	2,229
Admixed American	0.0333%	3,001
South Asian	0.0033%	30,347
European (non-Finnish)	0.000764%	130,927

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.Lys275=
Coding: c.825A>G
MANE Select: NM_170662
dbSNP: rs116564819
Type: single nucleotide variant
Location: chr3:105745937 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 275: the cbl-ptb domain; the 'sh2-like' region; a turn

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.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-lys275 (accessed [today's date]).

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