Is CBX7 p.Arg70Gly (c.208A>G) pathogenic?

CBX7 p.Arg70Gly (c.208A>G) is classified Uncertain significance in CBX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). AlphaMissense: likely pathogenic (0.788); Very rare (popmax 0.000169%, nfe).

How common is CBX7 p.Arg70Gly (c.208A>G) in the general population?

CBX7 p.Arg70Gly (c.208A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CBX7 p.Arg70Gly (c.208A>G)?

AlphaMissense predicts likely pathogenic (score 0.788) — an in-silico prediction, not a clinical call.

CBX7 p.Arg70Gly

c.208A>G · rs2518522568 · VCV2322018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.788 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.788	likely pathogenic
REVEL	0.272	benign-leaning
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.7, phastCons 1
Regional constraint	o/e 0.42	unconstrained · MANE · 14 kb · p 1e-09 · regional, not allelic
Overall
CADD	25.7	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 0.000169% European (non-Finnish) · 2/1,180,016 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,876 alleles · very rare

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: CBX7
Protein: p.Arg70Gly
Coding: c.208A>G
MANE Select: NM_175709
dbSNP: rs2518522568
Type: single nucleotide variant
Location: chr22:39138674 (GRCh38)
Gene constraint: LOEUF 0.767 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 67.01 · 9 PDB

Full CBX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBX7 p.Ala179Ser Uncertain significance ★ ⚠ same type
CBX7 p.Ala185Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala202Val Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Pro Uncertain significance ★ ⚠ same type
CBX7 p.Ala214Val Uncertain significance ★ ⚠ same type
CBX7 p.Arg140Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg159Cys Uncertain significance ★ ⚠ same type
CBX7 p.Arg170Gln 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/cbx7-p-arg70gly (accessed [today's date]).

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