Is CBLB p.Asp424= (c.1272C>T) pathogenic?

CBLB p.Asp424= (c.1272C>T) is classified Benign in CBLB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-06). Common (popmax 30.1%, amr) — too common for a highly-penetrant pathogenic allele; Associated with CBLB-related disorder.

What condition is associated with CBLB p.Asp424= (c.1272C>T)?

CBLB p.Asp424= (c.1272C>T) is associated with CBLB-related disorder (ClinVar).

CBLB p.Asp424=

Q: How common is CBLB p.Asp424= (c.1272C>T) in the general population?

CBLB p.Asp424= (c.1272C>T) is common (popmax 30.1%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1272C>T · rs2305035 · VCV3055764

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 30.1%, amr) — too common for a highly-penetrant pathogenic allele

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 1.6	GERP -1.1, phastCons 1
Overall
CADD	6.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% Admixed American · 18,008/59,882 alleles

Filtering AF 29.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.6%

Overall 21.9% 352,811/1,612,752 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	30.1%	3
Finnishnot grpmax-eligible	27.3%	4
Amishnot grpmax-eligible	24.2%	4
East Asian	23%	4
European (non-Finnish)	22.1%	5
Remaining individualsnot grpmax-eligible	21.5%	5
African / African-American	19.2%	5
Middle Eastern	14.7%	7
South Asian	14.5%	7
Ashkenazi Jewishnot grpmax-eligible	14.1%	7

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.Asp424=
Coding: c.1272C>T
MANE Select: NM_170662
dbSNP: rs2305035
Type: single nucleotide variant
Location: chr3:105720182 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 424: a β-strand

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.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-asp424 (accessed [today's date]).

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