Is CBLB p.Arg670Gln (c.2009G>A) pathogenic?

CBLB p.Arg670Gln (c.2009G>A) is classified Benign/Likely benign in CBLB (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-12-01). AlphaMissense: likely benign (0.2185); Low-frequency (popmax 1.49%, afr).

How common is CBLB p.Arg670Gln (c.2009G>A) in the general population?

CBLB p.Arg670Gln (c.2009G>A) is low-frequency (popmax 1.49%, afr) (gnomAD).

What do computational predictors say about CBLB p.Arg670Gln (c.2009G>A)?

AlphaMissense predicts likely benign (score 0.2185) — an in-silico prediction, not a clinical call.

CBLB p.Arg670Gln

c.2009G>A · rs114046756 · VCV786015

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2185 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2185	likely benign
REVEL	0.5	indeterminate
SaProt	LLR -6.74	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 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 45 kb · p 0.35 · regional, not allelic
Overall
CADD	25.8	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 1.49% African / African-American · 1,113/74,886 alleles

Filtering AF 1.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.38%

Overall 0.0745% 1,202/1,612,502 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.49%	67
Remaining individualsnot grpmax-eligible	0.0785%	1,274
Admixed American	0.0367%	2,725
Middle Eastern	0.0168%	5,968
South Asian	0.0033%	30,341
European (non-Finnish)	0.00119%	84,211

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.Arg670Gln
Coding: c.2009G>A
MANE Select: NM_170662
dbSNP: rs114046756
Type: single nucleotide variant
Location: chr3:105693539 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 670: a UniProt-annotated variant site (in admio3; likely pathogenic)

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

Similar variants

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
CBLB p.Ala928Val 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-arg670gln (accessed [today's date]).

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