Is CBLB p.Pro506= (c.1518C>T) pathogenic?

CBLB p.Pro506= (c.1518C>T) is classified Likely benign in CBLB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). Very rare (popmax 0.00667%, amr).

How common is CBLB p.Pro506= (c.1518C>T) in the general population?

CBLB p.Pro506= (c.1518C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

CBLB p.Pro506=

c.1518C>T · VCV3485651

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

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 -7.2	GERP -4
Overall
CADD	2.647	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00667% Admixed American · 4/60,000 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00347% 56/1,614,018 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	15,000
European (non-Finnish)	0.00415%	24,082
South Asian	0.00329%	30,359

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.Pro506=
Coding: c.1518C>T
MANE Select: NM_170662
Type: single nucleotide variant
Location: chr3:105704063 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 506: a UniProt-annotated variant site (in admio3; likely pathogenic); the 'disordered' region

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

Similar variants

CBLB p.Arg670Gln Benign/Likely benign ★★ same type
CBLB p.Pro387= Benign ★★ same type
CBLB p.Pro689= Benign/Likely benign ★★ same type
CBLB p.Ser622Thr Benign/Likely benign ★★ same type
CBLB c.2569+1609A>C Uncertain significance ★ same type
CBLB p.Ala176Pro Uncertain significance ★ ⚠ same type
CBLB p.Ala2Glu Uncertain significance ★ ⚠ same type
CBLB p.Ala592Ser 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/cblb-p-pro506 (accessed [today's date]).

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